ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.173G>A (p.Cys58Tyr)

gnomAD frequency: 0.00029  dbSNP: rs749920386
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000475170 SCV000547268 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 58 of the BRIP1 protein (p.Cys58Tyr). This variant is present in population databases (rs749920386, gnomAD 0.03%). 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: 407812). 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 RCV000575988 SCV000668904 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-26 criteria provided, single submitter clinical testing The p.C58Y variant (also known as c.173G>A), located in coding exon 2 of the BRIP1 gene, results from a G to A substitution at nucleotide position 173. The cysteine at codon 58 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is well 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.
Color Diagnostics, LLC DBA Color Health RCV000575988 SCV001351681 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-21 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 58 of the BRIP1 protein. Computational prediction tool 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 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 13/251388 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.
Baylor Genetics RCV003463894 SCV004214697 uncertain significance Familial cancer of breast 2023-11-18 criteria provided, single submitter clinical testing

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