Human Gene Module / Chromosome 10 / DIP2C

DIP2Cdisco interacting protein 2 homolog C

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 7
Rare Variants / Common Variants
29 / 0
Aliases
DIP2C, KIAA0934
Associated Syndromes
-
Chromosome Band
10p15.3
Associated Disorders
DD/NDD, ID
Relevance to Autism

A de novo loss-of-function (LoF) variant in the DIP2C gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF 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 two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), DIP2C was determined to be an ASD candidate gene in Yuen et al., 2017.

Molecular Function

This gene encodes a member of the disco-interacting protein homolog 2 family. The protein shares strong similarity with a Drosophila protein which interacts with the transcription factor disco and is expressed in the nervous system.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DIP2C (7 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) No -
2 Recent Recommendation Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support Autism risk in offspring can be assessed through quantification of male sperm mosaicism Breuss MW , et al. (2019) Yes -
4 Support - Cerminara M et al. (2021) Yes DD, ID
5 Support - Zhou X et al. (2022) Yes -
6 Support - Ashraf Yahia et al. (2024) No -
7 Recent Recommendation - Thoa Ha et al. (2024) No ASD, ADHD, ID, epilepsy/seizures
Rare Variants   (29)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.860-8C>T - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.398C>G p.Thr133Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3706A>C p.Met1236Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4094C>T p.Pro1365Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.820C>T p.Arg274Ter stop_gained De novo - Simplex 38421105 Thoa Ha et al. (2024)
c.4407C>T p.Ser1469%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1441C>T p.Arg481Ter stop_gained De novo - Unknown 38421105 Thoa Ha et al. (2024)
c.1598-2A>G - splice_site_variant Familial Paternal - 38421105 Thoa Ha et al. (2024)
c.3699C>G p.Tyr1233Ter stop_gained De novo - Unknown 38421105 Thoa Ha et al. (2024)
c.1385-2A>G - splice_site_variant De novo - Multiplex 38421105 Thoa Ha et al. (2024)
c.4045-2A>G - splice_site_variant Unknown - Multiplex 38421105 Thoa Ha et al. (2024)
c.4362-1G>A p.? splice_site_variant De novo - Simplex 38421105 Thoa Ha et al. (2024)
c.4615C>T p.Arg1539Ter stop_gained Familial Paternal - 38421105 Thoa Ha et al. (2024)
c.217C>G p.Arg73Gly missense_variant De novo - Simplex 38421105 Thoa Ha et al. (2024)
c.956C>T p.Ser319Leu missense_variant De novo - Unknown 38421105 Thoa Ha et al. (2024)
c.3757C>T p.Arg1253Ter stop_gained Familial Maternal Multiplex 38421105 Thoa Ha et al. (2024)
c.4045-5A>G - splice_region_variant Familial Maternal Multiplex 38421105 Thoa Ha et al. (2024)
GA>G p.Ser850ProfsTer10 frameshift_variant De novo - Simplex 31873310 Breuss MW , et al. (2019)
c.898dup p.Ala300GlyfsTer84 frameshift_variant De novo - Simplex 38421105 Thoa Ha et al. (2024)
c.467dup p.Ser157GlnfsTer53 frameshift_variant Familial Paternal - 38421105 Thoa Ha et al. (2024)
c.4028del p.Leu1343ArgfsTer14 frameshift_variant Familial Maternal - 38421105 Thoa Ha et al. (2024)
c.1969dup p.Ala657GlyfsTer12 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.757C>T p.Arg253Trp missense_variant Familial Maternal Simplex 33679889 Cerminara M et al. (2021)
c.2130_2131dup p.Ala711GlufsTer7 frameshift_variant De novo - Unknown 38421105 Thoa Ha et al. (2024)
c.636_637dup p.Tyr213CysfsTer39 frameshift_variant Familial - Simplex 28263302 C Yuen RK et al. (2017)
c.2208_2209dup p.Ala737ValfsTer15 frameshift_variant Familial Maternal - 38421105 Thoa Ha et al. (2024)
c.2208_2209del p.Ala737SerfsTer19 frameshift_variant De novo - Multiplex 38421105 Thoa Ha et al. (2024)
c.2208_2209dup p.Ala737ValfsTer15 frameshift_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.3062_3063insA p.His1023ProfsTer70 frameshift_variant Unknown - Multiplex 38300321 Ashraf Yahia et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo loss-of-function (LoF) variant in the DIP2C gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF 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 two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), DIP2C was determined to be an ASD candidate gene in Yuen et al., 2017.

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.

1/1/2021
2
icon
2

Score remained at 2

Description

A de novo loss-of-function (LoF) variant in the DIP2C gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF 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 two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), DIP2C was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[Case Report: Whole Exome Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient With Autism Spectrum Disorder, Intellectual Disability, Hyperactivity, Sleep and Gastrointestinal Distur2021]
1/1/2020
2
icon
2

Score remained at 2

Description

A de novo loss-of-function (LoF) variant in the DIP2C gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF 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 two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), DIP2C was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[Autism risk in offspring can be assessed through quantification of male sperm mosaicism.2019]
10/1/2019
2
icon
2

Score remained at 2

New Scoring Scheme
Description

A de novo loss-of-function (LoF) variant in the DIP2C gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF 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 two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), DIP2C was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[New Scoring Scheme]
4/1/2017
icon
2

Increased from to 2

Description

A de novo loss-of-function (LoF) variant in the DIP2C gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF 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 two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), DIP2C was determined to be an ASD candidate gene in Yuen et al., 2017.

Krishnan Probability Score

Score 0.61210857642934

Ranking 180/25841 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 0.9999998382774

Ranking 211/18225 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
Sanders TADA Score

Score 0.74109563056523

Ranking 1470/18665 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
Zhang D Score

Score 0.41891743440967

Ranking 1250/20870 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
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