ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.205C>A (p.Pro69Thr) (rs876658614)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221923 SCV000274104 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-13 criteria provided, single submitter clinical testing
GeneDx RCV000759586 SCV000293552 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.205C>A at the cDNA level, p.Pro69Thr (P69T) at the protein level, and results in the change of a Proline to a Threonine (CCA>ACA). Using alternate nomenclature, this variant would be defined as BRCA2 433C>A. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Pro69Thr was not observed in large population cohorts (Lek 2016). BRCA2 Pro69Thr 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 Pro69Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000689076 SCV000816714 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-25 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 69 of the BRCA2 protein (p.Pro69Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 230525). 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: "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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759586 SCV000888999 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing
Color RCV000221923 SCV000904866 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-16 criteria provided, single submitter clinical testing

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