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.

SFARI Genomic Platforms
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

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.

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.

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.
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
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).
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.
Submit New Gene

Report an Error