The c.5631_5635delinsA (p.Phe1877Leufs*39) variant in ATM is a frameshift variant predicted to cause a premature stop codon in a biologically-relevant-exon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant has been detected in at least four unrelated individuals with Ataxia-Telangiectasia (PMID: 15843990, 35260754, 2689183). The highest population minor allele frequency in gnomAD v4.1.0 is 0.0000064 in the South Asian population (PM2_Supporting, BS1, and BA1 are not met). 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. (PVS1, PM5_Supporting, PM3_VeryStrong)