ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.375T>A (p.Asp125Glu) (rs80358616)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132463 SCV000187557 likely benign Hereditary cancer-predisposing syndrome 2018-04-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113487 SCV000146704 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000132463 SCV000906877 likely benign Hereditary cancer-predisposing syndrome 2018-09-09 criteria provided, single submitter clinical testing
GeneDx RCV000603216 SCV000730232 likely benign not specified 2017-03-29 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.
Integrated Genetics/Laboratory Corporation of America RCV000588594 SCV000694717 uncertain significance not provided 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.375T>A (p.Asp125Glu) variant causes a missense change involving a non-conserved nucleotide with 3/5 in silico tools predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP). The variant of interest has been reported in one affected family via a publication, although with limited available information (ie lack of co-occurrence and cosegregation data). Multiple reputable clinical diagnostic laboratories/databases cite the variant with conflicting classifications "uncertain significance" or "likely benign." BIC reports the variant to co-occur with another pathogenic BRCA1 variant, c.5266dupC (p.Gln1756Profs - classified as pathogenic by LCA). Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

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