Submissions for variant NM_000059.4(BRCA2):c.5427C>T (p.Cys1809=)

gnomAD frequency: 0.00001  dbSNP: rs80359791

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113429	SCV000578988	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	RCV001088053	SCV000072670	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000164397	SCV000215033	likely benign	Hereditary cancer-predisposing syndrome	2014-11-19	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	RCV000443033	SCV000518432	benign	not specified	2015-08-17	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	RCV000164397	SCV000683705	benign	Hereditary cancer-predisposing syndrome	2016-10-08	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000113429	SCV000744470	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-06-28	criteria provided, single submitter	clinical testing
Counsyl	RCV000113429	SCV000786251	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-03-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757038	SCV000885089	likely benign	not provided	2017-12-03	criteria provided, single submitter	clinical testing	The BRCA2 c.5427C>T; p.Cys1809Cys variant is not published in the medical literature. The variant is listed in the ClinVar database (Variation ID: 51859), in the dbSNP variant database (rs80359791), and in the Genome Aggregation Database in 30/276920 alleles. This is a silent variant, the nucleotide at this position is not well conserved across species, and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) predict no significant change to splicing. Considering available information, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000757038	SCV001470225	likely benign	not provided	2020-05-01	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001088053	SCV002026119	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798235	SCV002043187	likely benign	Breast and/or ovarian cancer	2021-03-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164397	SCV002536139	likely benign	Hereditary cancer-predisposing syndrome	2021-07-09	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113429	SCV004016905	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542700	SCV004796986	likely benign	BRCA2-related disorder	2019-04-29	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	RCV000113429	SCV004846577	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-09-17	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113429	SCV000146612	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	1998-11-30	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000757038	SCV001905710	likely benign	not provided		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113429	SCV004243668	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing