Submissions for variant NM_000059.4(BRCA2):c.1272A>G (p.Ser424=)

gnomAD frequency: 0.00010  dbSNP: rs587780531

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000495562	SCV000578763	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086472	SCV000153819	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000163938	SCV000214534	likely benign	Hereditary cancer-predisposing syndrome	2014-08-22	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.
Color Diagnostics, LLC DBA Color Health	RCV000163938	SCV000683411	likely benign	Hereditary cancer-predisposing syndrome	2015-10-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781105	SCV000918940	likely benign	not specified	2019-08-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000119108	SCV001133674	benign	not provided	2023-05-08	criteria provided, single submitter	clinical testing
Mendelics	RCV000495562	SCV001138994	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000119108	SCV001898798	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001086472	SCV002026066	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163938	SCV002533222	likely benign	Hereditary cancer-predisposing syndrome	2022-01-12	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000495562	SCV004016832	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492510	SCV004240289	likely benign	Breast and/or ovarian cancer	2023-01-25	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000495562	SCV004846895	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2024-01-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004529990	SCV004754046	likely benign	BRCA2-related disorder	2019-11-05	no assertion criteria provided	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).