ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2582C>G (p.Ser861Cys)

gnomAD frequency: 0.00001  dbSNP: rs774415723
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167301 SCV000218144 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-22 criteria provided, single submitter clinical testing The p.S861C variant (also known as c.2582C>G), located in coding exon 18 of the BRIP1 gene, results from a C to G substitution at nucleotide position 2582. The serine at codon 861 is replaced by cysteine, an amino acid with dissimilar properties. This alteration has been reported in breast cancer and melanoma cohorts (Easton DF et al. J Med Genet, 2016 05;53:298-309; Potjer TP et al. Int J Cancer, 2019 05;144:2453-2464). 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 RCV000533602 SCV000633625 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 861 of the BRIP1 protein (p.Ser861Cys). This variant is present in population databases (rs774415723, gnomAD 0.003%). This missense change has been observed in individual(s) with personal and/or family history of breast cancer or melanoma (PMID: 26921362, 30414346). ClinVar contains an entry for this variant (Variation ID: 187562). 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.
Color Diagnostics, LLC DBA Color Health RCV000167301 SCV000909759 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-31 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 861 of the BRIP1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer and melanoma (PMID: 26921362, 30414346). This variant has been identified in 4/281246 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV004567340 SCV005059265 uncertain significance Familial cancer of breast 2024-02-05 criteria provided, single submitter clinical testing

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