ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.464G>C (p.Arg155Thr) (rs377639990)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656793 SCV000210242 uncertain significance not provided 2018-09-06 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.464G>C at the cDNA level, p.Arg155Thr (R155T) at the protein level, and results in the change of an Arginine to a Threonine (AGA>ACA). Using alternate nomenclature, this variant would be defined as BRCA2 692G>C. This variant has been observed in an individual with breast or ovarian cancer and an individual with low-grade glioma (Lu 2015, Azzollini 2016). BRCA2 Arg155Thr was not observed at a significant allele frequency in large population cohorts (Lek 2016This 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 Arg155Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000199441 SCV000254184 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 155 of the BRCA2 protein (p.Arg155Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs377639990, ExAC 0.002%). This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID:  27062684). ClinVar contains an entry for this variant (Variation ID: 37916). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160022 SCV000600599 uncertain significance not specified 2017-01-26 criteria provided, single submitter clinical testing
Color RCV000582907 SCV000688885 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031497 SCV000054102 uncertain significance Breast-ovarian cancer, familial 2 2010-05-05 no assertion criteria provided clinical testing

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