ClinVar

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants 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). 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. A different variant affecting this nucleotide (c.901+2T>A) has been reported in an individual with Ataxia Telangiectasia and been determined to be pathogenic (PMID: 10980530). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. This variant is also known as IVS9+2T>A in the literature. This variant has not been reported in the literature in individuals with ATM-related disease. This sequence change affects a donor splice site in intron 7 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.