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	2023-05-14	criteria provided, single submitter	clinical testing	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. Experimental studies have shown that this missense change does not substantially affect BRCA2 function (PMID: 29394989). 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. ClinVar contains an entry for this variant (Variation ID: 52478). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 20127978). This variant is not present in population databases (gnomAD no frequency). 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).
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