ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.848G>A (p.Cys283Tyr)

dbSNP: rs771096783
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV001169899 SCV001251961 uncertain significance Familial cancer of breast 2020-05-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002445406 SCV002677628 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-07 criteria provided, single submitter clinical testing The p.C283Y variant (also known as c.848G>A), located in coding exon 6 of the BRIP1 gene, results from a G to A substitution at nucleotide position 848. The cysteine at codon 283 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003769830 SCV004609360 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-11-02 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 283 of the BRIP1 protein (p.Cys283Tyr). This variant is present in population databases (rs771096783, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 915316). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRIP1 protein function with a positive predictive value of 80%. 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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