ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1552G>A (p.Val518Ile) (rs786201701)

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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 RCV000164112 SCV000214726 likely benign Hereditary cancer-predisposing syndrome 2019-09-17 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
GeneDx RCV000439785 SCV000515452 likely benign not specified 2017-08-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000475560 SCV000547228 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-07-17 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 518 of the BRIP1 protein (p.Val518Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 184796). 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 isoleucine 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. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000164112 SCV000909778 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000439785 SCV001338392 uncertain significance not specified 2020-02-25 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.1552G>A (p.Val518Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251388 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1552G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=1; VUS, n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.

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