Submissions for variant NM_000059.4(BRCA2):c.7182A>G (p.Arg2394=)

gnomAD frequency: 0.00001  dbSNP: rs80359797

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113717	SCV000578666	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics	RCV000568438	SCV000661261	likely benign	Hereditary cancer-predisposing syndrome	2016-02-29	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.
Color Diagnostics, LLC DBA Color Health	RCV000568438	SCV000689035	likely benign	Hereditary cancer-predisposing syndrome	2016-03-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586726	SCV000695048	likely benign	not specified	2019-03-26	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.7182A>G alters a non-conserved nucleotide resulting in a synonymous change. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246054 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7182A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.1961delA, p.Lys654SerfsX47), providing supporting evidence for a benign role. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1 VUS, 3 likely benign). Based on the evidence outlined above, the variant was classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001462194	SCV001666107	likely benign	Hereditary breast ovarian cancer syndrome	2024-08-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001540746	SCV001758664	likely benign	not provided	2019-09-20	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek 2016)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001540746	SCV002774127	likely benign	not provided	2021-07-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000113717	SCV004844370	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-11-20	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113717	SCV000147035	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2007-01-18	no assertion criteria provided	clinical testing