Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001027065 | SCV001189565 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-29 | criteria provided, single submitter | clinical testing | The c.8010G>A variant (also known as p.K2670K), located in coding exon 53 of the ATM gene, results from a G to A substitution at nucleotide position 8010. This nucleotide substitution does not change the lysine at 2670. However, this change occurs in the last base pair of coding exon 53, 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 predicts that this alteration will weaken the native splice donor site. 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. |
| Labcorp Genetics |
RCV001068502 | SCV001233618 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-11-13 | criteria provided, single submitter | clinical testing | This sequence change affects codon 2670 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. This variant also falls at the last nucleotide of exon 54, which is part of the consensus splice site for this exon. 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: 827395). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. |
| Gene |
RCV001564202 | SCV001787328 | uncertain significance | not provided | 2020-07-27 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003467696 | SCV004209547 | likely pathogenic | Familial cancer of breast | 2023-08-27 | criteria provided, single submitter | clinical testing |