Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221138 | SCV000278538 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-19 | criteria provided, single submitter | clinical testing | The p.G2644S variant (also known as c.7930G>A), located in coding exon 53 of the ATM gene, results from a G to A substitution at nucleotide position 7930. The glycine at codon 2644 is replaced by serine, an amino acid with similar properties. This alteration was observed in 0/7051 unselected female breast cancer patients, 0/11241 female controls, 0/53 unselected male breast cancer patients and 1/12490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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. |
| Color Diagnostics, |
RCV000221138 | SCV000911627 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-08 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with serine at codon 2644 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251236 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. |
| Labcorp Genetics |
RCV002516176 | SCV002968595 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2644 of the ATM protein (p.Gly2644Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 234050). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Baylor Genetics | RCV003469096 | SCV004209403 | uncertain significance | Familial cancer of breast | 2023-09-23 | criteria provided, single submitter | clinical testing |