ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2131A>G (p.Thr711Ala) (rs760515227)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526515 SCV000633593 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 711 of the BRIP1 protein (p.Thr711Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs760515227, ExAC 0.01%). This variant has been observed in an individual affected with hereditary breast and/or ovarian cancer (PMID: 28796317). ClinVar contains an entry for this variant (Variation ID: 461096). 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: "Deleterious"; 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.
Ambry Genetics RCV000568562 SCV000666178 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-18 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient evidence
Color RCV000568562 SCV000909768 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781187 SCV000919069 uncertain significance not specified 2018-12-04 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.2131A>G (p.Thr711Ala) results in a non-conservative amino acid change located in the ATP-dependent helicase, C-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245940 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.2131A>G, has been reported in the literature in one individual affected with Hereditary Breast and Ovarian Cancer with a strong family history (Sato_2017). These data do not allow any conclusion about variant significance. These data do not allow any conclusion about variant significance. Co-occurrences with other pathogenic variant(s) have been reported (APC c.4054_4063delGTTGAATTTT , p.Val1352fsX60), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030539 SCV001193535 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research

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