The NM_000152.5:c.2799+5G>A variant alters the splice donor region of intron 19, the last intron of GAA. The computational splicing predictor SpliceAI gives a score of 0.63 for donor loss, predicting that the variant disrupts the donor splice site of this intron (PP3). One patient, who is homozygous for the variant, has been described with clinical features consistent with Pompe disease and deficient activity of acid-glucosidase, specific values not provided (PM3_Supporting). This variant is absent in gnomAD v2.1.1. (PM2_Supporting). Additional variants in this splice region have been identified including c.2799+2C>A (classified by the ClinGen LD VCEP as a VUS), c.2799+2C>T (classified by the ClinGen LD VCEP as a VUS), and c.2799+4A>G (PMID: 26873529, 30564623; SpliceAI score = 0.62) (classified by the ClinGen LD VCEP as likely pathogenic) (PS1_Supporting based on a likely pathogenic variant in the same splice region; Walker et al, 2023; https://www.medrxiv.org/content/10.1101/2023.02.24.23286431v1) (PS1_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 2.0): PP3, PS1_Supporting, PM3_Supporting, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel, April 18, 2023).