Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014579 | SCV001175303 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-22 | criteria provided, single submitter | clinical testing | The c.2149C>A variant (also known as p.R717R), located in coding exon 13 of the ATM gene, results from a C to A substitution at nucleotide position 2149. This nucleotide substitution does not change the amino acid at codon 717. This nucleotide position is highly conserved in available vertebrate species. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV001044581 | SCV001208386 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change affects codon 717 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). 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: 820787). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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. |