ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7604G>A (p.Cys2535Tyr)

dbSNP: rs786203482
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166802 SCV000217616 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-23 criteria provided, single submitter clinical testing The p.C2535Y variant (also known as c.7604G>A), located in coding exon 14 of the BRCA2 gene, results from a G to A substitution at nucleotide position 7604. The cysteine at codon 2535 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507296 SCV000600759 uncertain significance not specified 2017-05-26 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000166802 SCV000905807 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000809247 SCV000949390 uncertain significance Hereditary breast ovarian cancer syndrome 2024-05-15 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 2535 of the BRCA2 protein (p.Cys2535Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 187112). 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 BRCA2 protein function with a negative predictive value of 95%. 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.
Myriad Genetics, Inc. RCV004019989 SCV004931816 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2024-03-27 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

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