Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000477608 | SCV000549799 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 409567). This missense change has been observed in individual(s) with Lynch syndrome (PMID: 25980754). This variant is present in population databases (rs770449225, gnomAD 0.007%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2997 of the BRCA2 protein (p.Tyr2997Cys). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758966 | SCV000887950 | uncertain significance | not provided | 2018-02-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001018593 | SCV001179849 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-19 | criteria provided, single submitter | clinical testing | The p.Y2997C variant (also known as c.8990A>G), located in coding exon 22 of the BRCA2 gene, results from an A to G substitution at nucleotide position 8990. The tyrosine at codon 2997 is replaced by cysteine, 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. |
| Gene |
RCV000758966 | SCV004021298 | uncertain significance | not provided | 2023-01-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 9218A>G; This variant is associated with the following publications: (PMID: 32377563, 31911673, 29884841, 29684080, 25980754, 12228710) |