Human Gene Module / Chromosome 14 / CHD8

CHD8chromodomain helicase DNA binding protein 8

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
48 / 74
Rare Variants / Common Variants
1 / 0
EAGLE Score
97.65
Strong Learn More
Aliases
CHD8, HELSNF1
Associated Syndromes
-
Chromosome Band
14q11.2
Associated Disorders
SCZ, DD/NDD, ADHD, ID, EPS, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

Recurrent mutations in the CHD8 gene have been identified in multiple individuals with ASD as described below. O'Roak et al., 2012a reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families (PMID 22495309). In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, O'Roak et al., 2012b identified 6 additional de novo CHD8 LoF mutations (PMID 23160995). A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in Iossifov et al., 2014 (PMID 25363768). Talkowski et al., 2012 (PMID 22521361) showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in Bernier et al., 2014 (PMID 24998929); a phenotypic comparison of patients with CHD8 variants in this report identified recurrent phenotypes and dysmorphic facial features suggestive of a syndromic form of ASD.

Molecular Function

This gene encodes a DNA helicase that functions as a transcription repressor by remodeling chromatin structure. It binds beta-catenin and negatively regulates Wnt signaling pathway, which plays a pivotal role in vertebrate early development and morphogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

SFARI Genomic Platforms
Reports related to CHD8 (74 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Novel deletions of 14q11.2 associated with developmental delay, cognitive impairment and similar minor anomalies in three children Zahir F , et al. (2007) No Cognitive impairment
2 Support CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome Batsukh T , et al. (2010) No -
3 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
4 Support Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries Talkowski ME , et al. (2012) Yes -
5 Support Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders O'Roak BJ , et al. (2012) Yes -
6 Support De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability McCarthy SE , et al. (2014) No -
7 Recent Recommendation Disruptive CHD8 mutations define a subtype of autism early in development Bernier R , et al. (2014) Yes DD, ID
8 Support Recurrent ?100 Kb microdeletion in the chromosomal region 14q11.2, involving CHD8 gene, is associated with autism and macrocephaly Prontera P , et al. (2014) Yes -
9 Recent Recommendation CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors Sugathan A , et al. (2014) No -
10 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
11 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
12 Support Recurrent de novo mutations implicate novel genes underlying simplex autism risk O'Roak BJ , et al. (2014) Yes -
13 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) Yes -
14 Recent Recommendation The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment Cotney J , et al. (2015) No -
15 Recent Recommendation The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes Wilkinson B , et al. (2015) No -
16 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
17 Support Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
18 Support Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms D'Gama AM , et al. (2015) Yes -
19 Support A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): A case report and literature review Merner N , et al. (2016) Yes ID, SCZ
20 Support Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay Smyk M , et al. (2016) No -
21 Support CHD8 intragenic deletion associated with autism spectrum disorder Stolerman ES , et al. (2016) Yes -
22 Support Identification of a rare variant in CHD8 that contributes to schizophrenia and autism spectrum disorder susceptibility Kimura H et al. (2016) No DD, ID, autistic features, stereotypy
23 Recent Recommendation Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling Durak O , et al. (2016) No -
24 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
25 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) Yes -
26 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) Yes -
27 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
28 Support Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism Chen R , et al. (2017) Yes -
29 Support Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability Tatton-Brown K , et al. (2017) No Macrocephaly, tall stature
30 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
31 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
32 Support Exome Pool-Seq in neurodevelopmental disorders Popp B , et al. (2017) No Autistic featues (social difficulties)
33 Recent Recommendation Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice Jung H , et al. (2018) No -
34 Support The autism spectrum phenotype in ADNP syndrome Arnett AB , et al. (2018) Yes ID
35 Support Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8 Marie C , et al. (2018) No -
36 Support Autism-linked CHD gene expression patterns during development predict multi-organ disease phenotypes Kasah S , et al. (2018) No -
37 Support Autism spectrum disorder early in development associated with CHD8 mutations among two Chinese children Wang J , et al. (2018) Yes -
38 Support Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing Wu J , et al. (2018) Yes -
39 Support Diagnostic approach with genetic tests for global developmental delay and/or intellectual disability: Single tertiary center experience Han JY et al. (2019) No -
40 Support Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder Du X , et al. (2018) Yes DD/ID
41 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
42 Support Targeted Next-Generation Sequencing of Korean Patients With Developmental Delay and/or Intellectual Disability Han JY , et al. (2019) No ADHD
43 Support A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8 Yasin H , et al. (2019) Yes -
44 Support The clinical presentation caused by truncating CHD8 variants Douzgou S , et al. (2019) Yes Macrocephaly
45 Support Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes Xiong J , et al. (2019) Yes ID
46 Support Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort Callaghan DB , et al. (2019) Yes -
47 Support Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population Monies D , et al. (2019) Yes ID, epilepsy/seizures
48 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing Aspromonte MC , et al. (2019) Yes -
49 Support Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans Wong WR , et al. (2019) Yes -
50 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
51 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
52 Support The CHD8 overgrowth syndrome: A detailed evaluation of an emerging overgrowth phenotype in 27 patients Ostrowski PJ , et al. (2019) No ASD, overgrowth
53 Support Genetic investigation of patients with tall stature Vasco de Albuquerque Albuquerque E et al. (2020) No Tall stature, macrocephaly
54 Support De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism Cappi C , et al. (2019) No -
55 Support De novo variants in the Helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth An Y , et al. (2020) Yes -
56 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
57 Support Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use Husson T , et al. (2020) Yes -
58 Support Genetic landscape of autism spectrum disorder in Vietnamese children Tran KT et al. (2020) Yes -
59 Support Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability Chevarin M et al. (2020) No Marfanoid habitus
60 Support A de novo variant of CHD8 in a patient with autism spectrum disorder Alotaibi M et al. (2020) No Autistic behavior, stereotypy
61 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
62 Recent recommendation - Sadler B et al. (2021) No ASD, DD
63 Support - Rodin RE et al. (2021) Yes -
64 Support - Brunet T et al. (2021) Yes -
65 Support - Kawamura A et al. (2021) Yes -
66 Support - Ellingford RA et al. (2021) Yes -
67 Recent Recommendation - Coll-Tané M et al. (2021) No -
68 Support - Doummar D et al. (2021) No ASD, ID
69 Support - Takanezawa Y et al. (2021) No -
70 Support - Mahjani B et al. (2021) Yes -
71 Recent Recommendation - Paulsen B et al. (2022) Yes -
72 Support - Chen X et al. (2022) No -
73 Support - Yu Y et al. (2022) Yes -
74 Support - Villa CE et al. (2022) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
1

Initial score established: 1

10/1/2021
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

7/1/2021
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

4/1/2021
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

1/1/2021
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

10/1/2020
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

7/1/2020
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

4/1/2020
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

1/1/2020
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

10/1/2019
1

Initial score established: 1

New Scoring Scheme
Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

7/1/2019
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

4/1/2019
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

1/1/2019
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

10/1/2018
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

7/1/2018
1S

Initial score established: 1S

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

4/1/2018
1.1 + S

Initial score established: 1.1 + S

Description

1S

1/1/2018
1S

Initial score established: 1S

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

10/1/2017
1

Initial score established: 1

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

7/1/2017
1S

Initial score established: 1S

Description

PMID 22495309 reported 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

4/1/2017
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Disruptive CHD8 mutations define a subtype of autism early in development.2014] [Recurrent 100 Kb microdeletion in the chromosomal region 14q11.2, involving CHD8 gene, is associated with autism and macrocephaly.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability.2014] [CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.2010] [CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.2014] [The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment.2015] [The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): A case report and literature review.2016] [Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay.2016] [CHD8 intragenic deletion associated with autism spectrum disorder.2016] [Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017]
1/1/2017
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

10/1/2016
1

Initial score established: 1

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

7/1/2016
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

4/1/2016
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

1/1/2016
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Disruptive CHD8 mutations define a subtype of autism early in development.2014] [Recurrent 100 Kb microdeletion in the chromosomal region 14q11.2, involving CHD8 gene, is associated with autism and macrocephaly.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability.2014] [CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.2010] [CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.2014] [The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment.2015] [The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): A case report and literature review.2016] [Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay.2016] [CHD8 intragenic deletion associated with autism spectrum disorder.2016]
10/1/2015
1

Initial score established: 1

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD.

7/1/2015
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD.

4/1/2015
1S

Initial score established: 1S

Description

PMID 22495309 showed 2 de novo loss-of-function (LoF) mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LoF mutations. A ninth de novo LoF variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LoF variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A phenotypic comparison of patients with CHD8 variants in PMID 24998929 identified recurrent dysmorphic facial features suggestive of a syndromic form of ASD.

1/1/2015
1

Initial score established: 1

Description

PMID 22495309 showed 2 de novo LGD mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LGD mutations. A ninth de novo LGD variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LGD variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

10/1/2014
1

Initial score established: 1

Description

PMID 22495309 showed 2 de novo LGD mutations in CHD8 among 209 simplex ASD families. In a screen of 44 genes in 2,446 ASD probands from the Simons Simplex Collection, PMID 23160955 found 6 additional de novo CHD8 LGD mutations. A ninth de novo LGD variant in CHD8 in an ASD proband from the Simons Simplex Collection was observed in PMID 25363768. Additional LGD variants in CHD8 were identified in children with developmental delay and ASD in PMID 24998929. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified CHD8 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

7/1/2014
1

Initial score established: 1

Description

PMID 22495309 showed 2 de novo LGD mutations in CHD8 among 209 ASD families. PMID 22495311 reported 3 additional CHD8 LGD mutations in 935 cases and none among 870 controls. In a screen of 44 genes in 2,446 ASD probands, PMID 23160955 found 9 additional de novo CHD8 LGD mutations. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders.

4/1/2014
1

Initial score established: 1

Description

PMID 22495309 showed 2 de novo LGD mutations in CHD8 among 209 ASD families. PMID 22495311 reported 3 additional CHD8 LGD mutations in 935 cases and none among 870 controls. In a screen of 44 genes in 2,446 ASD probands, PMID 23160955 found 9 additional de novo CHD8 LGD mutations. PMID 22521361 showed that CHD8 is among 33 loci with balanced chromosomal abnormalities in individuals with ASD or other neurodevelopmental disorders.

Krishnan Probability Score

Score 0.48605406881788

Ranking 7247/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.99999999999809

Ranking 45/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Iossifov Probability Score

Score 0.998

Ranking 7/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Sanders TADA Score

Score 3.056711550542E-10

Ranking 1/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score

Score 262

Ranking 2/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.43689316255242

Ranking 1064/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
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