Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000579673 | SCV000683968 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194437 | SCV001363997 | uncertain significance | not specified | 2019-04-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.8485C>A (p.Gln2829Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246072 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8485C>A has been reported in the literature in a study involving individuals affected with male breast cancer (Rizzolo 2008). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A co-occurrence with a pathogenic variant has been reported in the UMD database (BRCA2 c.3847_3848delGT, p.Val1283fsX2). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV000579673 | SCV002681601 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-20 | criteria provided, single submitter | clinical testing | The p.Q2829K variant (also known as c.8485C>A), located in coding exon 18 of the BRCA2 gene, results from a C to A substitution at nucleotide position 8485. The glutamine at codon 2829 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV002529092 | SCV002993186 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-04-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 2829 of the BRCA2 protein (p.Gln2829Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30613976). ClinVar contains an entry for this variant (Variation ID: 489789). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |