Submissions for variant NM_000059.4(BRCA2):c.8032A>G (p.Arg2678Gly)

dbSNP: rs80359039

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000045394	SCV000073407	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-02-26	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2678 of the BRCA2 protein (p.Arg2678Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 20127978). ClinVar contains an entry for this variant (Variation ID: 52478). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33609447) indicates that this missense variant is not expected to disrupt BRCA2 function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA2 function (PMID: 29394989). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000572606	SCV000661365	likely benign	Hereditary cancer-predisposing syndrome	2019-12-06	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.
Counsyl	RCV000077424	SCV000786212	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2018-03-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001588866	SCV001826752	uncertain significance	not provided	2019-10-02	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in an individual with early onset breast cancer (Lee 2008); Also known as BRCA2 8260A>G; This variant is associated with the following publications: (PMID: 29884841, 31131967, 18284688, 19043619, 29394989, 20127978)
Baylor Genetics	RCV004566846	SCV005059195	uncertain significance	Familial cancer of breast	2023-11-09	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000077424	SCV000109222	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2009-06-29	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000077424	SCV000147253	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496893	SCV000587932	uncertain significance	not specified	2014-01-31	no assertion criteria provided	research