ClinVar Miner

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

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044616 SCV000072629 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000165821 SCV000216568 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-21 criteria provided, single submitter clinical testing The p.R174H variant (also known as c.521G>A), located in coding exon 6 of the BRCA2 gene, results from a G to A substitution at nucleotide position 521. The arginine at codon 174 is replaced by histidine, an amino acid with highly similar properties. This variant was also observed in 1/1469 population-based female breast cancer patients diagnosed between the ages of 20 and 49 years and has been observed in a patient with breast cancer who had another BRCA2 variant (Lee E et al. Breast Cancer Res. 2008; 10(1):R19, Wárlám-Rodenhuis CC et al. Eur. J. Cancer. 2005 Jul; 41(10):1409-15). An in vitro minigene assay showed increased skipping of coding exon 6 (Di Giacomo D et al. Hum. Mutat. 2013 Nov; 34(11):1547-57); however multiple additional studies using patient derived material have shown that this alteration does not result in an appreciable amount of aberrant splicing (Ambry internal data, Houdayer C et al. Hum. Mutat. 2012 Aug; 33(8):1228-38). This amino acid position is well conserved in a limited alignment of available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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 Health, Inc RCV000165821 SCV000902941 likely benign Hereditary cancer-predisposing syndrome 2016-03-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985540 SCV001133821 uncertain significance not provided 2019-03-08 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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