ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6513G>T (p.Val2171=) (rs206076)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495019 SCV000579088 likely benign Breast-ovarian cancer, familial 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/).
GeneDx RCV000168590 SCV000210629 benign not specified 2014-09-22 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.
Ambry Genetics RCV000163332 SCV000213866 likely benign Hereditary cancer-predisposing syndrome 2014-09-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724515 SCV000225154 uncertain significance not provided 2017-02-13 criteria provided, single submitter clinical testing
Invitae RCV001080322 SCV000253026 benign Hereditary breast and ovarian cancer syndrome 2020-11-17 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163332 SCV000683789 likely benign Hereditary cancer-predisposing syndrome 2016-10-01 criteria provided, single submitter clinical testing
Counsyl RCV000495019 SCV000786526 likely benign Breast-ovarian cancer, familial 2 2018-05-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000724515 SCV000889100 benign not provided 2018-12-04 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353822 SCV000592060 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Val2171Val variant was not identified in the literature, but it was identified in dbSNP (ID: rs206076) “With benign, uncertain significance and untested allele”, Clinvitae database 4X, the ClinVar database with conflicting significance (1X as benign, 1X as likely benign and 2X as uncertain significance), UMD 2X an unknown variantand the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 4 of 10278 chromosomes (frequency: 0.00038) from a population of African individuals and in 3 of 66608 chromosomes (frequency: 4.50 X 10-3) from a population of European (Non-Finnish) individuals, although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in our laboratory with a co-occurring pathogenic BRCA2 variant (p.Phe1559LeufsX9), increasing the likelihood that the p.Val2171Val variant does not have clinical significance. The p.Val2171Val 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 summary, based on the above information, we lean towards a more benign role for this variant. This variant is classified as benign.

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