DYNC1H1dynein cytoplasmic 1 heavy chain 1
Autism Reports / Total Reports
15 / 23Rare Variants / Common Variants
36 / 0Aliases
DYNC1H1, CMT2O, DHC1, DHC1a, DNCH1, DNCL, DNECL, DYHC, Dnchc1, HL-3, SMALED1, p22Associated Syndromes
-Chromosome Band
14q32.31Associated Disorders
ID, ASD, EPSGenetic Category
Rare Single Gene Mutation, SyndromicRelevance to Autism
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score >2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Two de novo missense variants in DYNC1H1 that had previously been identified in ASD probands in De Rubeis et al., 2014 and Krumm et al., 2015 were determined to be postzygotic mosaic mutations in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 21/84,448 expected; hypergeometric P-value of 8.8E-03).
Molecular Function
This gene encodes a member of the cytoplasmic dynein heavy chain family. Dyneins are a group of microtubule-activated ATPases that function as molecular motors. Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
Reports related to DYNC1H1 (23 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | A de novo paradigm for mental retardation | Vissers LE , et al. (2010) | No | - |
2 | Support | Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects | Willemsen MH , et al. (2012) | No | - |
3 | Primary | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
4 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
5 | Support | Excess of rare, inherited truncating mutations in autism | Krumm N , et al. (2015) | Yes | - |
6 | Recent Recommendation | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
7 | Support | Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies | Lin Z , et al. (2017) | No | West syndrome |
8 | Support | Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism | Chen R , et al. (2017) | Yes | - |
9 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | No | - |
10 | Recent Recommendation | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
11 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
12 | Support | Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice | Tumien B , et al. (2017) | Yes | - |
13 | Support | Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes | Guo H , et al. (2018) | Yes | - |
14 | Support | The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children | Long S , et al. (2019) | Yes | - |
15 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
16 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
17 | Support | DYNC1H1-related disorders: A description of four new unrelated patients and a comprehensive review of previously reported variants | Amabile S et al. (2020) | No | ASD, ID, epilepsy/seizures |
18 | Support | - | Rodin RE et al. (2021) | Yes | - |
19 | Support | - | Pode-Shakked B et al. (2021) | No | - |
20 | Support | - | Mahjani B et al. (2021) | Yes | - |
21 | Support | - | Yang H et al. (2021) | No | - |
22 | Support | - | ÃÂlvarez-Mora MI et al. (2022) | No | - |
23 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
Rare Variants (36)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.3960+1G>A | - | splice_site_variant | De novo | NA | - | 31139143 | Long S , et al. (2019) | |
c.3278T>C | p.Phe1093Ser | missense_variant | De novo | NA | - | 34803881 | Yang H et al. (2021) | |
c.3351C>G | p.Asn1117Lys | missense_variant | De novo | NA | - | 34803881 | Yang H et al. (2021) | |
c.5884C>T | p.Arg1962Cys | missense_variant | De novo | NA | - | 34803881 | Yang H et al. (2021) | |
c.4741A>C | p.Lys1581Gln | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.5096A>G | p.Asn1699Ser | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.9418C>T | p.Arg3140Trp | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.9521G>A | p.Arg3174His | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.11084G>A | p.Arg3695Gln | missense_variant | De novo | NA | - | 33432195 | Rodin RE et al. (2021) | |
c.6994C>T | p.Arg2332Cys | missense_variant | De novo | NA | - | 29286531 | Tumien B , et al. (2017) | |
c.3347T>C | p.Val1116Ala | missense_variant | De novo | NA | - | 32656949 | Amabile S et al. (2020) | |
c.4234C>T | p.His1412Tyr | missense_variant | De novo | NA | - | 32656949 | Amabile S et al. (2020) | |
c.4532C>T | p.Pro1511Leu | missense_variant | De novo | NA | - | 32656949 | Amabile S et al. (2020) | |
c.2363A>G | p.Tyr788Cys | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
c.12315G>A | p.Trp4105Ter | stop_gained | De novo | NA | Simplex | 28344757 | Chen R , et al. (2017) | |
c.10973G>A | p.Gly3658Glu | missense_variant | De novo | NA | - | 32656949 | Amabile S et al. (2020) | |
c.4396-1G>C | - | splice_site_variant | De novo | NA | Multiplex | 32094338 | Husson T , et al. (2020) | |
c.2467G>T | p.Val823Leu | missense_variant | De novo | NA | - | 25363760 | De Rubeis S , et al. (2014) | |
c.10573C>T | p.Arg3525Cys | missense_variant | De novo | NA | - | 28554332 | Bowling KM , et al. (2017) | |
c.6698C>T | p.Ala2233Val | missense_variant | De novo | NA | - | 25363760 | De Rubeis S , et al. (2014) | |
c.7718A>G | p.Asp2573Gly | missense_variant | De novo | NA | - | 25363760 | De Rubeis S , et al. (2014) | |
c.925C>T | p.Arg309Cys | missense_variant | De novo | NA | Simplex | 25961944 | Krumm N , et al. (2015) | |
c.12797A>T | p.Asn4266Ile | missense_variant | De novo | NA | - | 25363760 | De Rubeis S , et al. (2014) | |
c.4552G>A | p.Glu1518Lys | missense_variant | De novo | NA | - | 22368300 | Willemsen MH , et al. (2012) | |
c.10174A>G | p.Met3392Val | missense_variant | De novo | NA | Simplex | 28325891 | Lin Z , et al. (2017) | |
c.13088A>C | p.Lys4363Thr | missense_variant | De novo | NA | Simplex | 30504930 | Guo H , et al. (2018) | |
c.9073G>A | p.Glu3025Lys | missense_variant | De novo | NA | Simplex | 28263302 | C Yuen RK et al. (2017) | |
c.6258T>C | p.Tyr2086%3D | synonymous_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
c.9192C>T | p.Val3064%3D | synonymous_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
c.12315G>A | p.Trp4105Ter | stop_gained | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.12214G>A | p.Gly4072Ser | missense_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.11465A>C | p.His3822Pro | missense_variant | De novo | NA | Simplex | 21076407 | Vissers LE , et al. (2010) | |
c.9209C>T | p.Pro3070Leu | missense_variant | De novo | NA | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
c.3072A>G | p.Thr1024= | synonymous_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.4462dup | p.Arg1488ProfsTer5 | frameshift_variant | Familial | Maternal | - | 35183220 | ÃÂlvarez-Mora MI et al. (2022) | |
c.10213A>C | p.Met3405Leu | missense_variant | De novo | NA | Multiplex (dizygotic twins) | 34803881 | Yang H et al. (2021) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
Score Delta: Decreased from 3 to 1
criteria met
See SFARI Gene'scoring criteriaWe 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.
10/1/2021

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
7/1/2021

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
4/1/2021

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
1/1/2021

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
10/1/2020

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
7/1/2020

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
4/1/2020

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
1/1/2020

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
10/1/2019

Decreased from 3 to 1
New Scoring Scheme
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
Reports Added
[New Scoring Scheme]7/1/2019

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
4/1/2019

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
1/1/2019

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
10/1/2018

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
7/1/2018

Decreased from 4.4 + acc2 to 3
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
4/1/2018

Increased from 3 to 4.4 + acc2
Description
3
10/1/2017

Decreased from 3 to 1
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
4/1/2017

Increased from to 3
Description
De novo missense variants in the DYNC1H1 gene have previously been identified in ASD cases (De Rubeis et al., 2014; Iossifov et al., 2014). An additional de novo missense variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple de novo missense variants in ASD cases, a z-score >2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), DYNC1H1 was determined to be an ASD candidate gene in Yuen et al., 2017. Whole exome sequencing in 116 ASD parent-proband trios as part of the University of Illinois at Chicago ACE project identified a de novo nonsense variant in DYNC1H1 in one ASD proband (Chen et al., 2017). Mutations in the DYNC1H1 gene are associated with autosomal dominant mental retardation-13 (MRD13; OMIM 614563), a form of intellectual disability associated with variable neuronal migration defects resulting in cortical malformations (Vissers et al., 2010; Willemsen et al., 2012).
Krishnan Probability Score
Score 0.49505790574011
Ranking 3234/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 1
Ranking 12/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.909
Ranking 126/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.57467998807286
Ranking 631/18665 scored genes
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Zhang D Score
Score 0.17111697182878
Ranking 4778/20870 scored genes
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