The c.8045C>G variant in ATM is a missense variant predicted to cause substitution of threonine by serine at amino acid 2682 (p.Thr2682Ser). This variant has been detected in individual(s) with Ataxia-Telangiectasia (PMID: 12815592). The highest population minor allele frequency in gnomAD v4.1.0 is 0.0.00002229 (1/44868alleles) in East Asian population; while this is higher than the HBOP VCEP threshold (≤0.00001) for PM2_Supporting, it is present in only one allele, meeting this criterion. The computational splicing predictor SpliceAI gives a score of 0.97 for donor gain, predicting that the variant disrupts the donor splice site of ATM. RNA analysis demonstrated that this variant leads to partial skipping of exon 54, resulting in an in-frame deletion (removes amino acids 2681-2717) that is predicted to escape nonsense mediated decay but adversely impact the FATKIN domain (Ambry internal data). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant ATM-related cancer predisposition and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied as specified by the HBOP VCEP. (PM3_Supporting, PM2_Supporting, PVS1[RNA]).