ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2623G>C (p.Glu875Gln) (rs876659099)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223507 SCV000275149 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-23 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000231669 SCV000291019 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 875 of the BRIP1 protein (p.Glu875Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine. 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: 231332). 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.
Integrated Genetics/Laboratory Corporation of America RCV001174776 SCV001338105 uncertain significance not specified 2020-01-23 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.2623G>C (p.Glu875Gln) 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 allele was found at a frequency of 1.1e-05 in 261556 control chromosomes (gnomAD and publication). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2623G>C has been reported in the literature in one individual affected with breast cancer and/or ovarian cancer (Schubert_2019). The report does not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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