Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000509846 | SCV000608256 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-19 | criteria provided, single submitter | clinical testing | The p.T3413K variant (also known as c.10238C>A), located in coding exon 26 of the BRCA2 gene, results from a C to A substitution at nucleotide position 10238. The threonine at codon 3413 is replaced by lysine, an amino acid with similar properties. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003389648 | SCV000694501 | uncertain significance | not specified | 2023-10-16 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.10238C>A (p.Thr3413Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250592 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10238C>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (VUS, n=2; Likely benign: n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV000698928 | SCV000827619 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 3413 of the BRCA2 protein (p.Thr3413Lys). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 441516). 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. |
Color Diagnostics, |
RCV000509846 | SCV000906629 | likely benign | Hereditary cancer-predisposing syndrome | 2016-06-28 | criteria provided, single submitter | clinical testing |