Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000773723 | SCV000907423 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000773723 | SCV002671084 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-16 | criteria provided, single submitter | clinical testing | The c.73-3delC intronic variant, located in intron 1 of the ATM gene, results from a deletion of one nucleotide within intron 1 of the ATM gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003605684 | SCV004405342 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 629036). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 2 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within 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. |
| Institute for Biomarker Research, |
RCV000773723 | SCV005688907 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-01-03 | criteria provided, single submitter | clinical testing | The splice region variant NM_000051.4(ATM):c.73-3delC has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.73-3delC variant is novel (not in any individuals) in gnomAD. The c.73-3delC variant is novel (not in any individuals) in 1kG. The c.73-3delC variant is not predicted to disrupt the existing acceptor splice site 1bp upstream by 3 of 4 splice site algorithms. For these reasons, this variant has been classified as Uncertain Significance. |