Human Gene Module / Chromosome 10 / WDFY4

WDFY4WDFY family member 4

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
6 / 0
Aliases
WDFY4, C10orf64
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
10q11.23
Associated Disorders
-
Relevance to Autism

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

Molecular Function

Reports related to WDFY4 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
2 Support Genome-wide characteristics of de novo mutations in autism. Yuen RK , et al. (2016) Yes -
3 Support Prevalence and architecture of de novo mutations in developmental disorders. Deciphering Developmental Disorders Study (2017) No -
4 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
5 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity. Coe BP , et al. (2018) No -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
delC - frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.8519C>T p.Pro2840Leu missense_variant De novo - Simplex 27525107 Yuen RK , et al. (2016)
c.908C>T p.Ser303Leu missense_variant De novo - Multiplex 28263302 C Yuen RK , et al. (2017)
c.5387C>A p.Ala1796Asp missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.7546C>A p.Leu2516Met missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.7414C>T p.Arg2472Trp missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

Score Delta: Score remained at 3

2

Strong Candidate

See all Category 2 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.

7/1/2019
3
icon
3

Score remained at 3

Description

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

1/1/2019
icon
3

Increased from to 3

Description

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

Krishnan Probability Score

Score 0.47560107230917

Ranking 8561/25841 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.
Sanders TADA Score

Score 0.94554151576874

Ranking 16511/18665 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).
Zhang D Score

Score 0.007773966940073

Ranking 8437/20870 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.
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