Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000815087 | SCV000955530 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-07-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 658289). 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 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. This variant is also known as IVS30‚àí2A>G. This sequence change affects an acceptor splice site in intron 28 of the ATM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with early-onset breast cancer (PMID: 12362033). |
| Ambry Genetics | RCV003362973 | SCV004054040 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-11 | criteria provided, single submitter | clinical testing | The c.4237-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 28 in the ATM gene. This alteration, designated as IVS30-2A>G, has been reported in an individual with a personal history of breast cancer diagnosed before age 40 (Maillet P et al. J Med Genet, 2002 Oct;39:751-3). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004569708 | SCV005056997 | pathogenic | Familial cancer of breast | 2024-02-11 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000815087 | SCV002081689 | likely pathogenic | Ataxia-telangiectasia syndrome | 2021-07-12 | no assertion criteria provided | clinical testing |