Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000408965 | SCV000487068 | likely pathogenic | Ataxia-telangiectasia syndrome | 2016-10-03 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000408965 | SCV000838571 | likely pathogenic | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000408965 | SCV000941678 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-08-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 371475). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 35264596). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 43 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). |
| Ambry Genetics | RCV002365447 | SCV002657295 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-17 | criteria provided, single submitter | clinical testing | The c.6348-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 43 of the ATM gene. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This nucleotide position is well 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. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Baylor Genetics | RCV003470352 | SCV004210063 | likely pathogenic | Familial cancer of breast | 2023-08-08 | criteria provided, single submitter | clinical testing |