Human Gene Module / Chromosome 2 / DNMT3A

DNMT3ADNA (cytosine-5-)-methyltransferase 3 alpha 

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
7 / 0
Aliases
DNMT3A, DNMT3A2,  M.HsaIIIA,  TBRS
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
2p23.3
Associated Disorders
-
Relevance to Autism

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Molecular Function

The protein encoded by this gene is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It plays a role in paternal and maternal imprinting.

Reports related to DNMT3A (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Jiang YH , et al. (2013) Yes -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
4 Primary Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Sanders SJ , et al. (2015) Yes -
5 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
6 Support Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose... Farwell Hagman KD , et al. (2016) No -
7 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1903C>T p.Arg635Trp missense_variant De novo - Simplex 23849776 Jiang YH , et al. (2013)
c.2204A>G p.Tyr735Cys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.403insA p.Gly135fs frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.2711C>T p.Pro904Leu missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.1993G>T p.Val665Leu missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.2644C>T p.Arg882Cys missense_variant De novo - - 27479843 Lelieveld SH , et al. (2016)
- p.Gly298Trp missense_variant De novo - - 27513193 Farwell Hagman KD , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

04-01-2017
CNVs associated with DNMT3A(1 CNVs)
2p23.3 10 Deletion 18  /  65
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