Submissions for variant NM_003072.5(SMARCA4):c.715G>A (p.Gly239Ser)

dbSNP: rs761515593

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228181	SCV000286138	likely benign	Rhabdoid tumor predisposition syndrome 2	2024-11-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000561121	SCV000664041	likely benign	Hereditary cancer-predisposing syndrome	2019-02-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab	RCV001808649	SCV002057984	likely benign	Intellectual disability, autosomal dominant 16	2021-07-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003390988	SCV004120610	uncertain significance	SMARCA4-related disorder	2023-06-14	criteria provided, single submitter	clinical testing	The SMARCA4 c.715G>A variant is predicted to result in the amino acid substitution p.Gly239Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-11097224-G-A), which is likely too common for an undocumented disease-causing variant. In ClinVar, this variant is interpreted as likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/238514/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477813	SCV004221247	uncertain significance	not provided	2022-11-17	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00036 (8/22456 chromosomes in South Asian subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
GeneDx	RCV003477813	SCV005079386	uncertain significance	not provided	2023-12-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge