Submissions for variant NM_000059.4(BRCA2):c.6271A>C (p.Ser2091Arg)

gnomAD frequency: 0.00001  dbSNP: rs398122550

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129368	SCV000184132	likely benign	Hereditary cancer-predisposing syndrome	2019-02-01	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227893	SCV000283287	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000438559	SCV000512378	likely benign	not specified	2018-01-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000129368	SCV000688973	likely benign	Hereditary cancer-predisposing syndrome	2017-03-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985562	SCV001133858	uncertain significance	not provided	2024-12-05	criteria provided, single submitter	clinical testing	The BRCA2 c.6271A>C (p.Ser2091Arg) variant has been identified in the published literature in a reportedly healthy individual (PMID: 32467295 (2020)). In addition, this variant has been reported to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). The frequency of this variant in the general population, 0.000024 (3/126850 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000129368	SCV003852377	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000438559	SCV004804379	uncertain significance	not specified	2024-01-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000076958	SCV004846728	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-12-18	criteria provided, single submitter	clinical testing
Genomics and Molecular Medicine Service, East Genomic Laboratory Hub, NHS Genomic Medicine Service	RCV004691747	SCV005196378	likely benign	Inherited breast cancer and ovarian cancer	2024-06-26	criteria provided, single submitter	clinical testing	BP1,BP4
Sharing Clinical Reports Project (SCRP)	RCV000076958	SCV000108755	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-07	no assertion criteria provided	clinical testing