Human Gene Module / Chromosome 12 / SMARCC2

SMARCC2SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 2

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
5 / 0
Aliases
SMARCC2, BAF170,  CRACC2,  Rsc8
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Chromosome Band
12q13.2
Associated Disorders
EPS
Relevance to Autism

A de novo splice-site variant in this gene was identified in a simplex ASD proband (Neale et al., 2012). The protein encoded by the SMARCC2 gene interacts with the protein encoded by the high-confidence ASD gene ADNP (Mandel and Gozes, 2007).

Molecular Function

The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors.

Reports related to SMARCC2 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex. Mandel S and Gozes I (2007) No -
2 Primary Patterns and rates of exonic de novo mutations in autism spectrum disorders. Neale BM , et al. (2012) Yes -
3 Support De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
4 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
5 Recent recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia. Takata A , et al. (2016) No -
6 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. Martnez F , et al. (2016) No Epilepsy/seizures
7 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
8 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1863+1C>A;c.1770+1C>A - splice_site_variant De novo - Simplex 22495311 Neale BM , et al. (2012)
c.3372G>C p.(=) synonymous_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.1311-3C>G - splice_site_variant De novo - - 27620904 Martnez F , et al. (2016)
c.1179+2T>A p.? splice_site_variant Unknown Not maternal - 27824329 Wang T , et al. (2016)
c.1555C>T p.Arg519Ter stop_gained De novo - Simplex 28263302 C Yuen RK , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo LoF variant in this gene was identified in an ASD proband from the Autism Sequencing Consortium (Neale et al., 2012). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A second de novo LoF variant in this gene was identified in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of two de novo LoF variants in this gene in ASD probands, a probability of LoF intolerance rate (pLI) > 0.9, and higher-than-expected mutation rate (false discovery rate < 15%), SMARCC2 was determined to be an ASD candidate gene in Yuen et al., 2017.

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.

04-01-2017
2

Initial score established: 2

Description

A de novo LoF variant in this gene was identified in an ASD proband from the Autism Sequencing Consortium (Neale et al., 2012). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A second de novo LoF variant in this gene was identified in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of two de novo LoF variants in this gene in ASD probands, a probability of LoF intolerance rate (pLI) > 0.9, and higher-than-expected mutation rate (false discovery rate < 15%), SMARCC2 was determined to be an ASD candidate gene in Yuen et al., 2017.

CNVs associated with SMARCC2(1 CNVs)
12q13.2 6 Deletion 11  /  23
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