ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2477A>G (p.Asn826Ser) (rs760127237)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000582319 SCV000689337 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587241 SCV000699697 uncertain significance not provided 2016-11-10 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.2477A>G (p.Asn826Ser) variant located in the P-loop containing nuceloside triphosphate hydrolase domain (via InterPro) causes a missense change involving a conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured here due to low reliability index) predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/119650, which does not exceed the estimated maximal expected allele frequency for a pathogenic BRIP1 variant of 1/16000. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, until additional information becomes available, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
Invitae RCV000541763 SCV000633614 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-26 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 826 of the BRIP1 protein (p.Asn826Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs760127237, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 461111). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.

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