Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492899 | SCV000581440 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-18 | criteria provided, single submitter | clinical testing | The p.R2832P variant (also known as c.8495G>C), located in coding exon 57 of the ATM gene, results from a G to C substitution at nucleotide position 8495. The arginine at codon 2832 is replaced by proline, an amino acid with dissimilar properties. This alteration has been identified in trans with a second ATM alteration in two brothers with clinical characteristics of ataxia telangiectasia (internal data). 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 majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV002527069 | SCV003446452 | likely pathogenic | Ataxia-telangiectasia syndrome | 2022-07-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant disrupts the p.Arg2832 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9443866, 10817650, 10873394, 12552559, 18634022, 19431188, 26681312). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 429065). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 2832 of the ATM protein (p.Arg2832Pro). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |