ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.487C>T (p.Pro163Ser) (rs1064795902)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483934 SCV000572138 uncertain significance not provided 2018-10-03 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.487C>T at the cDNA level, p.Pro163Ser (P163S) at the protein level, and results in the change of a Proline to a Serine (CCC>TCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Pro163Ser was not observed in large population cohorts (Lek 2016). This variant is located in the nuclear localization signal (Cantor 2011). 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 BRIP1 Pro163Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565081 SCV000668905 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-23 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000811860 SCV000952149 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-10-20 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 163 of the BRIP1 protein (p.Pro163Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 422627). 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 serine amino acid residue is 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 and their clinical significance is uncertain. 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.
Color RCV000565081 SCV001352854 likely benign Hereditary cancer-predisposing syndrome 2017-01-22 criteria provided, single submitter clinical testing

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