Submissions for variant NM_000059.4(BRCA2):c.8090G>A (p.Ser2697Asn)

gnomAD frequency: 0.00005  dbSNP: rs80359051

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081007	SCV000073433	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000129422	SCV000184192	benign	Hereditary cancer-predisposing syndrome	2020-02-29	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000203629	SCV000210666	likely benign	not provided	2021-06-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26689913, 28111427, 19043619, 25111659, 20104584, 28324225, 25348012, 20167696, 32444794, 29884841, 27535533, 12228710, 31131967)
Michigan Medical Genetics Laboratories, University of Michigan	RCV000083143	SCV000267816	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000203629	SCV000600783	likely benign	not provided	2020-01-07	criteria provided, single submitter	clinical testing
Counsyl	RCV000083143	SCV000784898	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2017-02-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129422	SCV000910968	benign	Hereditary cancer-predisposing syndrome	2016-01-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000045420	SCV000918918	benign	not specified	2022-01-17	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.8090G>A (p.Ser2697Asn) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 251314 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (4e-05 vs 0.00075), allowing no conclusion about variant significance. c.8090G>A has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with one pathogenic variant have been reported in multiple individuals (BRCA2 c.1800T>G, p.Tyr600Ter, BIC and UMD databases; BRCA1, c.2138C>G, p.Ser713Ter, internal database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign/likely benign n=7, VUS n=3). Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000203629	SCV001746177	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	BRCA2: BP1, BP4
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000203629	SCV002010318	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798239	SCV002043503	uncertain significance	Breast and/or ovarian cancer	2019-07-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000045420	SCV002069624	likely benign	not specified	2019-08-30	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000045420	SCV005090057	benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000083143	SCV000115217	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000083143	SCV000147271	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000203629	SCV001906149	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000203629	SCV001957482	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000203629	SCV001972497	likely benign	not provided		no assertion criteria provided	clinical testing
Center for Precision Medicine, Meizhou People's Hospital	RCV001762154	SCV002520839	likely benign	Familial cancer of breast		no assertion criteria provided	literature only