ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9019A>G (p.Arg3007Gly) (rs397507417)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167398 SCV000218253 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160163 SCV000592249 uncertain significance not specified 2014-11-06 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000160163 SCV000588125 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735617 SCV000863755 uncertain significance Breast and/or ovarian cancer 2009-07-23 no assertion criteria provided clinical testing
GeneDx RCV000766653 SCV000210492 uncertain significance not provided 2018-07-11 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9019A>G at the cDNA level, p.Arg3007Gly (R3007G) at the protein level, and results in the change of an Arginine to a Glycine (AGA>GGA). Using alternate nomenclature, this variant would be defined as BRCA2 9247A>G. This variant was reported in one breast cancer case and did not fully segregate with breast cancer in this family; however, the individual with the earliest onset of disease was not tested (Cavallone 2010). Additionally, BRCA2 Arg3007Gly showed an intermediate performance in a homologous recombination DNA-repair assay (Guidugli 2018). This variant was not observed in large population cohorts (Lek 2016). BRCA2 Arg3007Gly is located in the DNA binding domain (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA2 Arg3007Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000167961 SCV000218609 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-05-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 3007 of the BRCA2 protein (p.Arg3007Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant was observed in a single family affected with breast cancer, but there is insufficient evidence to conclude whether or not it segregates with disease (PMID: 20694749). ClinVar contains an entry for this variant (Variation ID: 38203). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031786 SCV000054394 uncertain significance Breast-ovarian cancer, familial 2 2008-03-19 no assertion criteria provided clinical testing

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