Submissions for variant NM_000059.4(BRCA2):c.10023C>T (p.Asp3341=)

gnomAD frequency: 0.00001  dbSNP: rs113507014

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000495017	SCV000578919	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	RCV000164212	SCV000214833	likely benign	Hereditary cancer-predisposing syndrome	2015-06-28	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	RCV001079160	SCV000560417	benign	Hereditary breast ovarian cancer syndrome	2024-01-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759569	SCV000888965	likely benign	not provided	2022-12-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164212	SCV000906830	likely benign	Hereditary cancer-predisposing syndrome	2017-12-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194385	SCV001363891	likely benign	not specified	2019-04-22	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.10023C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 250960 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.10023C>T has not been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories and one expert panel have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. In addition, a reputable database indicates the variant to co-occur with a pathogenic BRCA1 variant, c.5152+5G>A (internally classified as pathogenic). Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx	RCV000759569	SCV001857650	benign	not provided	2015-03-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17724471)
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001079160	SCV002025887	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000759569	SCV005042168	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	BRCA2: BP4, BP7
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000759569	SCV001905725	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000759569	SCV001952397	likely benign	not provided		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000495017	SCV004243887	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing