Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000387350 | SCV000330736 | likely pathogenic | not provided | 2016-08-15 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.663-2A>G or IVS6-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 6 of the ATM gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature. Based on the currently available information, we consider ATM c.663-2A>G to be a likely pathogenic variant. |
Counsyl | RCV000669607 | SCV000794378 | likely pathogenic | Ataxia-telangiectasia syndrome | 2017-10-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000669607 | SCV001576515 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-08-27 | 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: 280786). 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 6 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 | RCV002374450 | SCV002667283 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | The c.663-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 6 in the ATM gene. 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. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |