ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1748A>G (p.Lys583Arg)

gnomAD frequency: 0.00001  dbSNP: rs876658547
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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 RCV000222420 SCV000273941 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-20 criteria provided, single submitter clinical testing The p.K583R variant (also known as c.1748A>G), located in coding exon 11 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1748. The lysine at codon 583 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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 RCV000535277 SCV000633571 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 583 of the BRIP1 protein (p.Lys583Arg). This variant is not present in population databases (gnomAD no frequency). 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: 230402). 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 not expected to disrupt BRIP1 protein function with a negative 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 RCV000222420 SCV000684156 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-30 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 583 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
GeneDx RCV001753660 SCV002005574 uncertain significance not provided 2019-08-19 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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