ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.409A>G (p.Lys137Glu)

dbSNP: rs878855157
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000227127 SCV000291049 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-09-29 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 137 of the BRIP1 protein (p.Lys137Glu). 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: 241660). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV000576071 SCV000666242 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-02 criteria provided, single submitter clinical testing The p.K137E variant (also known as c.409A>G), located in coding exon 4 of the BRIP1 gene, results from an A to G substitution at nucleotide position 409. The lysine at codon 137 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been reported with a carrier frequency of 0.00000 in 7636 unselected prostate cancer patients and 0.00016 in 12366 male controls of Japanese ancestry (Momozawa Y et al. J Natl Cancer Inst, 2020 04;112:369-376). This alteration was also identified in a cohort of patients diagnosed with biliary tract carcinoma undergoing multigene panel testing for hereditary cancer risk (Terashima T et al. Oncotarget, 2019 Oct;10:5949-5957). 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.
Color Diagnostics, LLC DBA Color Health RCV000576071 SCV000905248 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-13 criteria provided, single submitter clinical testing
GeneDx RCV001194700 SCV001826498 uncertain significance not provided 2023-11-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31214711, 36243179, 31666926)
Leiden Open Variation Database RCV001194700 SCV001364457 uncertain significance not provided 2019-08-13 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

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