Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001911628 | SCV002168187 | pathogenic | Ataxia-telangiectasia syndrome | 2021-01-29 | criteria provided, single submitter | clinical testing | This sequence change affects donor splice site in intron 42 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 (ExAC no frequency). Variants affecting this donor splice site have been observed as homozygous or in combination with another ATM variant in several individuals affected with ataxia telangiectasia (PMID: 9463314, 21459046, 26915675, 26220245). In addition, they have been reported as heterozygous in individuals affected with ATM-related cancers (PMID: 29909963, 16832357, 21792198). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |