Submissions for variant NM_003072.5(SMARCA4):c.2085C>T (p.Ser695=)

gnomAD frequency: 0.00018  dbSNP: rs149342641

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000349254	SCV000410481	benign	Coffin-Siris syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000469124	SCV000559403	likely benign	Rhabdoid tumor predisposition syndrome 2	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000573038	SCV000663946	likely benign	Hereditary cancer-predisposing syndrome	2015-11-17	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.
GeneDx	RCV001582969	SCV001814012	likely benign	not provided	2020-12-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001582969	SCV001961770	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	SMARCA4: BP4, BP7
Genome-Nilou Lab	RCV001808757	SCV002057066	likely benign	Intellectual disability, autosomal dominant 16	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000573038	SCV002532814	benign	Hereditary cancer-predisposing syndrome	2020-12-01	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002480162	SCV002773983	benign	not specified	2021-08-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003969933	SCV004783797	likely benign	SMARCA4-related disorder	2021-12-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).