Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130175 | SCV000185012 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-14 | criteria provided, single submitter | clinical testing | The p.R2191G variant (also known as c.6571A>G), located in coding exon 44 of the ATM gene, results from an A to G substitution at nucleotide position 6571. The arginine at codon 2191 is replaced by glycine, an amino acid with dissimilar properties. This alteration was identified in a cohort of patients with myeloid malignancy who underwent WES (Li ST et al. Leukemia, 2020 06;34:1675-1678). This amino acid position is 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. |
| Gene |
RCV000212045 | SCV000209764 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in 3/60466 cases and 1/53461 controls in a breast cancer case-control study (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 33471991, 23532176, 31911633) |
| Color Diagnostics, |
RCV000130175 | SCV000682352 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-17 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glycine at codon 2191 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a large international case-control study, this variant was reported in 3/60463 breast cancer cases and 1/53460 controls (PMID: 33471991). This variant has been identified in 1/251460 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 |
RCV000628002 | SCV000748889 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2191 of the ATM protein (p.Arg2191Gly). This variant is present in population databases (rs587781861, gnomAD 0.0009%). 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: 141591). 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. |
| Sema4, |
RCV000130175 | SCV002538293 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-15 | criteria provided, single submitter | curation |