Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000494252 | SCV000581442 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-13 | criteria provided, single submitter | clinical testing | The p.G2925V variant (also known as c.8774G>T), located in coding exon 59 of the ATM gene, results from a G to T substitution at nucleotide position 8774. The glycine at codon 2925 is replaced by valine, an amino acid with dissimilar properties. This alteration was previously reported in at least one individual from a cohort of 278 BRCA1/2-negative individuals with early-onset breast cancer via multiplex panel testing of 22 cancer susceptibility genes (Maxwell KN et al. Genet. Med., 2015 Aug;17:630-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Color Diagnostics, |
RCV000494252 | SCV000682514 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001865534 | SCV002238636 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-02-20 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with breast cancer (PMID: 25503501). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2925 of the ATM protein (p.Gly2925Val). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 429066). 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. |