ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.521G>A (p.Arg174His) (rs80358747)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044616 SCV000072629 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 174 of the BRCA2 protein (p.Arg174His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs80358747, ExAC 0.006%). This variant has been reported in the literature in individuals affected with breast cancer (PMID: 15955690, 18284688). ClinVar contains an entry for this variant (Variation ID: 51825). In an experimental study, this variant was reported to cause a splicing defect resulting in the skipping of exon 7 at low levels (PMID: 23983145) but in another report, alternative splicing was not detected (PMID: 22505045). The clinical significance of these results is not known. Algorithms developed to predict the effect of missense changes on protein structure and function also do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000165821 SCV000216568 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000427870 SCV000512332 likely benign not specified 2017-06-27 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.
Color RCV000165821 SCV000902941 likely benign Hereditary cancer-predisposing syndrome 2016-03-05 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083114 SCV000115188 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083114 SCV000147063 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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