ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1594A>G (p.Met532Val) (rs876658383)

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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 RCV000214562 SCV000273521 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-18 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000532257 SCV000633562 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-08-06 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 532 of the BRIP1 protein (p.Met532Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 230095). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Color RCV000214562 SCV000684140 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780069 SCV000917091 uncertain significance not specified 2018-12-26 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.1594A>G (p.Met532Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 246136 control chromosomes (gnomAD). 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.1594A>G 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. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Leiden Open Variation Database RCV001194750 SCV001364526 uncertain significance not provided 2019-03-03 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.

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