Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001027230 | SCV001189748 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-18 | criteria provided, single submitter | clinical testing | The c.8151G>A variant (also known as p.K2717K), located in coding exon 54 of the ATM gene, results from a G to A substitution at nucleotide position 8151. This nucleotide substitution does not change the amino acid at codon 2717. However, this change occurs in the last base pair of coding exon 54, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Color Diagnostics, |
RCV001027230 | SCV001342031 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001207545 | SCV001378905 | pathogenic | Ataxia-telangiectasia syndrome | 2025-01-26 | criteria provided, single submitter | clinical testing | This sequence change affects codon 2717 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 likely results in a shortened 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: 827482). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 55, but is expected to preserve the integrity of the reading-frame (internal data). This variant disrupts a region of the ATM protein in which other variant(s) (p.Asp2708Asn) have been determined to be pathogenic (PMID: 16941484, 21665257, 22071889, 23632773). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |