ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7605T>G (p.Cys2535Trp)

gnomAD frequency: 0.00001  dbSNP: rs966152147
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000469552 SCV000549533 uncertain significance Hereditary breast ovarian cancer syndrome 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 2535 of the BRCA2 protein (p.Cys2535Trp). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 409443). 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 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.
GeneDx RCV000480630 SCV000570136 uncertain significance not provided 2020-08-07 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV000570362 SCV000661370 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-02 criteria provided, single submitter clinical testing The p.C2535W variant (also known as c.7605T>G), located in coding exon 14 of the BRCA2 gene, results from a T to G substitution at nucleotide position 7605. The cysteine at codon 2535 is replaced by tryptophan, 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.
Color Diagnostics, LLC DBA Color Health RCV000570362 SCV001350543 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-22 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tryptophan at codon 2535 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been identified in 2/250774 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 RCV003463914 SCV004216132 uncertain significance Familial cancer of breast 2024-03-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000808 SCV004844439 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tryptophan at codon 2535 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been identified in 2/250774 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005239033 SCV005885067 uncertain significance not specified 2024-12-19 criteria provided, single submitter clinical testing

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