Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000456342 | SCV000547343 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 848 of the BRIP1 protein (p.Arg848Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 30093976, 34326862). ClinVar contains an entry for this variant (Variation ID: 407850). 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. |
| Ambry Genetics | RCV000570309 | SCV000661599 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-27 | criteria provided, single submitter | clinical testing | The p.R848C variant (also known as c.2542C>T), located in coding exon 17 of the BRIP1 gene, results from a C to T substitution at nucleotide position 2542. The arginine at codon 848 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was identified in 1/5242 controls but not in 13,213 cases from a population-based case-control study of breast cancer in the United Kingdom (Easton DF et al. J. Med. Genet., 2016 May;53:298-309). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477950 | SCV004220704 | uncertain significance | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 30093976 (2018)). In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer as well as in an unaffected individual (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRIP1)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Baylor Genetics | RCV004568009 | SCV005059916 | uncertain significance | Familial cancer of breast | 2023-12-31 | criteria provided, single submitter | clinical testing |