Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001213644 | SCV001385288 | likely pathogenic | Ataxia-telangiectasia syndrome | 2022-07-05 | 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: 943453). 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 affects an acceptor splice site in intron 60 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). |
MGZ Medical Genetics Center | RCV002290641 | SCV002579552 | likely pathogenic | Familial cancer of breast | 2021-12-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002375176 | SCV002685139 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-13 | criteria provided, single submitter | clinical testing | The c.8787-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 60 in the ATM gene. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that a different nucleotide change impacting this splice site, c.8787-1G>C, 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 a disease-causing mutation. |
Baylor Genetics | RCV002290641 | SCV004213941 | likely pathogenic | Familial cancer of breast | 2021-12-23 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV002290641 | SCV004931787 | likely pathogenic | Familial cancer of breast | 2024-02-05 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |