ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.341A>G (p.His114Arg) (rs80358586)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568060 SCV000661258 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000113436 SCV000146621 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000568060 SCV000903162 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-26 criteria provided, single submitter clinical testing
GeneDx RCV000214245 SCV000279503 uncertain significance not provided 2018-05-04 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.341A>G at the cDNA level, p.His114Arg (H114R) at the protein level, and results in the change of a Histidine to an Arginine (CAT>CGT). Using alternate nomenclature, this variant would be defined as BRCA2 569A>G. This variant was observed in at least one woman with early onset breast cancer (Haffty 2009). BRCA2 His114Arg was observed at an allele frequency of 0.04% (8/22,204) in individuals of Finnish ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 His114Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000044189 SCV000072202 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 114 of the BRCA2 protein (p.His114Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs80358586, ExAC 0.03%). This variant has been reported in an individual affected with breast cancer (PMID: 19491284). ClinVar contains an entry for this variant (Variation ID: 51460). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The arginine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000214245 SCV000887790 uncertain significance not provided 2018-06-23 criteria provided, single submitter clinical testing

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