Submissions for variant NM_000059.4(BRCA2):c.5688A>G (p.Ala1896=)

gnomAD frequency: 0.00002  dbSNP: rs768907899

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000211036	SCV000579091	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/).
Ambry Genetics	RCV000163288	SCV000213816	likely benign	Hereditary cancer-predisposing syndrome	2014-11-03	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.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000211036	SCV000267784	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-21	criteria provided, single submitter	clinical testing
Invitae	RCV001079723	SCV000283269	benign	Hereditary breast ovarian cancer syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163288	SCV000683725	likely benign	Hereditary cancer-predisposing syndrome	2016-01-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587180	SCV000694891	likely benign	not provided	2016-04-04	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.5688A>G variant affects a non-conserved nucleotide, resulting in no amino acid change. Mutation Taster predicts a benign outcome for this variant, 4/5 Alamut algorithms no change to splice sites, and there are no predicted changes to ESEs. This variant was found in 2/120666 control chromosomes at a frequency of 0.0000166, which does not significantly exceed maximal expected frequency of a pathogenic BRCA2 allele (0.0007503). However, one clinical lab classifies the variant as likely benign (without evidence to independently evaluate), and the variant was reported to co-occur with a pathogenic BRCA1 variant (p.Arg1203X) in one individual from the UMD database. This variant has several supporting evidence lines for a benign outcome, thus in accordance with ACMG guidelines, this BRCA2 synonymous variant was classified as likely benign.
GeneDx	RCV000615328	SCV000730834	benign	not specified	2015-04-21	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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000211036	SCV000743311	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000211036	SCV000744474	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587180	SCV002047321	likely benign	not provided	2023-05-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163288	SCV002536163	likely benign	Hereditary cancer-predisposing syndrome	2021-10-19	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV000211036	SCV004846624	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-11-02	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000211036	SCV000733271	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000163288	SCV000787936	likely benign	Hereditary cancer-predisposing syndrome	2017-09-11	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000587180	SCV001906388	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000587180	SCV001959564	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000587180	SCV002035565	likely benign	not provided		no assertion criteria provided	clinical testing