Human Gene Module / Chromosome 5 / YTHDC2

YTHDC2YTH domain containing 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
9 / 1
Aliases
YTHDC2, CAHL
Associated Syndromes
-
Chromosome Band
5q22.2
Associated Disorders
-
Relevance to Autism

Rare and potentially damaging de novo missense variants in the YTHDC2 gene have been identified in individuals with ASD (ORoak et al., 2012; De Rubeis et al., 2014). A SNP downstream of the YTHDC2 gene (rs2170527, minor allele C) was found to associate with ASD in a case-control analysis of Japanese ASD cases and controls (Odds ratio 2.602, 95% CI 1.75-3.87, P-value 1.12E-06) in Liu et al., 2016.

Molecular Function

Probable ATP-dependent RNA helicase

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to YTHDC2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Positive Association Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations Liu X , et al. (2015) Yes -
4 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
5 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Wang J et al. (2023) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Maternal Simplex 22495309 O'Roak BJ , et al. (2012)
c.315A>G p.Lys105%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.206_208del p.Ser69del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
c.2444C>T p.Thr815Ile missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.3079A>G p.Ile1027Val missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.549A>G p.Glu183%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1434A>G p.Leu478= synonymous_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.724C>T p.Arg242Cys missense_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.3723A>G p.Lys1241%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - intergenic_variant - - - 26314684 Liu X , et al. (2015)
SFARI Gene score
2

Strong Candidate

Rare and potentially damaging de novo missense variants in the YTHDC2 gene have been identified in individuals with ASD (ORoak et al., 2012; De Rubeis et al., 2014). A SNP downstream of the YTHDC2 gene (rs2170527, minor allele C) was found to associate with ASD in a case-control analysis of Japanese ASD cases and controls (Odds ratio 2.602, 95% CI 1.75-3.87, P-value 1.12E-06) in Liu et al., 2016.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Rare and potentially damaging de novo missense variants in the YTHDC2 gene have been identified in individuals with ASD (ORoak et al., 2012; De Rubeis et al., 2014). A SNP downstream of the YTHDC2 gene (rs2170527, minor allele C) was found to associate with ASD in a case-control analysis of Japanese ASD cases and controls (Odds ratio 2.602, 95% CI 1.75-3.87, P-value 1.12E-06) in Liu et al., 2016.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare and potentially damaging de novo missense variants in the YTHDC2 gene have been identified in individuals with ASD (ORoak et al., 2012; De Rubeis et al., 2014). A SNP downstream of the YTHDC2 gene (rs2170527, minor allele C) was found to associate with ASD in a case-control analysis of Japanese ASD cases and controls (Odds ratio 2.602, 95% CI 1.75-3.87, P-value 1.12E-06) in Liu et al., 2016.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

Rare and potentially damaging de novo missense variants in the YTHDC2 gene have been identified in individuals with ASD (ORoak et al., 2012; De Rubeis et al., 2014). A SNP downstream of the YTHDC2 gene (rs2170527, minor allele C) was found to associate with ASD in a case-control analysis of Japanese ASD cases and controls (Odds ratio 2.602, 95% CI 1.75-3.87, P-value 1.12E-06) in Liu et al., 2016.

Krishnan Probability Score

Score 0.44508008238033

Ranking 15575/25841 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.
Original Source
ExAC Score

Score 0.99999957170434

Ranking 255/18225 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
Original Source
Iossifov Probability Score

Score 0.895

Ranking 151/239 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
Original Source
Sanders TADA Score

Score 0.84484323482004

Ranking 3286/18665 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).
Original Source
Larsen Cumulative Evidence Score

Score 5

Ranking 297/461 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.
Original Source
Zhang D Score

Score 0.52619871990968

Ranking 351/20870 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.
Original Source
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
FGF3 Fibroblast growth factor 3 Human Protein Binding 2248 P11487
FGF8 Fibroblast growth factor 8 Human Protein Binding 2253 P55075-2
HCVgp1 N/A Human Protein Binding 951475 B8Y460
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