ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1715T>G (p.Val572Gly)

dbSNP: rs1603334516
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000811857 SCV000952146 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-06-10 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 572 of the BRIP1 protein (p.Val572Gly). 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: 655636). 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.
Ambry Genetics RCV002397671 SCV002712314 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-24 criteria provided, single submitter clinical testing The p.V572G variant (also known as c.1715T>G), located in coding exon 11 of the BRIP1 gene, results from a T to G substitution at nucleotide position 1715. The valine at codon 572 is replaced by glycine, an amino acid with dissimilar properties. This variant was also observed in 1/3251 individuals who met eligibility criteria for hereditary breast and ovarian cancer syndrome (Lerner-Ellis J et al. J Cancer Res Clin Oncol, 2021 Mar;147:871-879). This amino acid position is not well 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.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355454 SCV001550342 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The BRIP1 p.Val572Gly variant was not identified in the literature nor was it identified in the dbSNP or ClinVar databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The p.Val572Gly residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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