ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4314C>T (p.Val1438=) (rs730881590)

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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) RCV000494781 SCV000578784 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 RCV000160223 SCV000210604 benign not specified 2014-06-28 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 RCV000163622 SCV000214190 likely benign Hereditary cancer-predisposing syndrome 2014-09-30 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.
Invitae RCV001079328 SCV000253014 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163622 SCV000683610 likely benign Hereditary cancer-predisposing syndrome 2016-04-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587498 SCV000694765 likely benign not provided 2017-01-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4314C>T (p.Val1438Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation Taster predicts a damaging outcome for this variant. This variant does not overlap a splice site and Alamut 5/5 splicing tools predict no major changes caused by the variant. ESEfinder predicts a loss of binding motif for splicing enhancer SRp55. This variant was found in 5/119340 control chromosomes at a frequency of 0.0000419, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Publications (Ikediobi_Mol Cancer Ther_2006 and Stordal_Mol Oncol_2013) listed variant as polymorphism identified in an ovarian tumor cell line. The variant was identified as a somatic mutation in one colorectal tumor (Giannakis_NG_2014), but has not been cited as a germline mutation in patients from the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Benign/Likely Benign. Taken together, this variant is classified as Likely Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587498 SCV000887810 likely benign not provided 2020-06-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283318 SCV001160589 likely benign none provided 2019-08-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160223 SCV000591901 benign not specified no assertion criteria provided clinical testing This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. In addition, it has been identified in one individual who also carried a pathogenic mutation in the BRCA2 gene, increasing the likelihood that this variant is benign. In summary, based on the above information, this variant is classified as benign.

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