Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214628 | SCV000278267 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-07 | criteria provided, single submitter | clinical testing | The p.R459G variant (also known as c.1375A>G), located in coding exon 9 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1375. The arginine at codon 459 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000694775 | SCV000823233 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 459 of the BRIP1 protein (p.Arg459Gly). This variant is present in population databases (rs752052351, gnomAD 0.01%). 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: 233813). 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. |
Color Diagnostics, |
RCV000214628 | SCV001349800 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-27 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glycine at codon 459 of the BRIP1 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/279280 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. |
Genetic Services Laboratory, |
RCV001818542 | SCV002068117 | uncertain significance | not specified | 2020-04-22 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003463592 | SCV004214760 | uncertain significance | Familial cancer of breast | 2023-09-08 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477766 | SCV004220683 | uncertain significance | not provided | 2022-11-03 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.0000072 (2/279280 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer (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 predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |