Submissions for variant NM_000059.4(BRCA2):c.8702G>A (p.Gly2901Asp)

gnomAD frequency: 0.00004  dbSNP: rs80359129

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001084578	SCV000073618	benign	Hereditary breast ovarian cancer syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000130464	SCV000185329	likely benign	Hereditary cancer-predisposing syndrome	2019-02-22	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	RCV000590249	SCV000210479	likely benign	not provided	2021-02-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26757417, 23108138, 19043619, 28277317, 14973102, 18607349, 9579822, 24323938, 22486713, 18627636, 18779604, 26221963, 11251181, 28222693, 29394989, 26848529, 29681614, 24817641, 31131967, 29884841, 31825140)
Color Diagnostics, LLC DBA Color Health	RCV000130464	SCV000683993	benign	Hereditary cancer-predisposing syndrome	2016-03-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590249	SCV000695176	likely benign	not provided	2016-05-02	criteria provided, single submitter	clinical testing	Variant summary: The c.8702G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Asp. 4/4 in-silico tools predict damaging outcome for this variant. This variant is found in 14/121646 control chromosomes from ExAC at a frequency of 0.0001151. It was predominantly reported in East Asian subpopulation with an allele frequency of 0.0016 which is about 2.15 times higher than the maximum expected allele frequency of a pathogenic variant in this gene suggesting that it is likely to be a polymorphism in East Asians. The variant has been reported in several breast and/or ovarian cancer patients/families, mainly of East Asian origin, without strong evidence for pathogenicity. In one patient with thyroid and breast cancer, a truncating mutation PTEN c. 590delA was also found, possibly suggesting for an alternative disease mechanism. In addition, it was also found in once in each of benign breast cancer patient and healthy control cohorts, possibly suggesting a benign outcome. Functional studies (HDR, cell viability and drug sensitivity assays) shows neutral outcome for this variant. Three out of five clinical labs have also classified this variant as likely benign/benign (other two as uncertain significance). Taken together, this variant has currently been classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000590249	SCV001133946	benign	not provided	2018-09-07	criteria provided, single submitter	clinical testing
Mendelics	RCV000031763	SCV001139225	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818200	SCV002068243	likely benign	not specified	2019-01-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532461	SCV004710855	likely benign	BRCA2-related disorder	2022-01-25	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).
All of Us Research Program, National Institutes of Health	RCV000031763	SCV004846059	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-06-08	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031763	SCV000054371	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2010-01-22	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031763	SCV000147441	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2000-06-12	flagged submission	clinical testing
Counsyl	RCV000031763	SCV000487777	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2015-11-25	flagged submission	clinical testing
Center for Precision Medicine, Meizhou People's Hospital	RCV002250495	SCV002520845	likely benign	Familial cancer of breast		no assertion criteria provided	literature only
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153312	SCV003843612	likely pathogenic	Ovarian cancer	2022-01-01	flagged submission	clinical testing