Submissions for variant NM_000059.4(BRCA2):c.8061T>C (p.Val2687=)

gnomAD frequency: 0.00001  dbSNP: rs776992904

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000495042	SCV000578856	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	RCV000164091	SCV000214702	likely benign	Hereditary cancer-predisposing syndrome	2014-08-21	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	RCV001081404	SCV000283331	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-11	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589034	SCV000600781	likely benign	not provided	2023-02-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164091	SCV000689094	likely benign	Hereditary cancer-predisposing syndrome	2017-08-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000506599	SCV000695124	likely benign	not specified	2019-08-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000589034	SCV001888369	benign	not provided	2015-09-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000495042	SCV004845594	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-22	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000589034	SCV000778715	likely benign	not provided	2018-01-02	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356773	SCV001552033	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRCA2 p.Val2687= variant was not identified in the literature nor was it identified in the LOVD 3.0, BIC Database, ARUP Laboratories, or Zhejiang Colon Cancer Databases. The variant was identified in dbSNP (ID: rs776992904) as With Likely benign allele, ClinVar (classified as likely benign by ENIGMA, Ambry Genetics, Invitae), Clinvitae (classified as likely benign ClinVar), the COGR (conflicting interpretations of pathogenicity), and UMD-LSDB (2X unclassified variant). The variant was identified in control databases in 1 of 246044 chromosomes at a frequency of 0.000004 (Genome Aggregation Consortium Feb 27, 2017). The p.Val2687= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004539541	SCV004768674	likely benign	BRCA2-related disorder	2020-02-18	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).