Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001789727 | SCV002032127 | pathogenic | Glycogen storage disease, type II | 2021-08-19 | reviewed by expert panel | curation | The c.1057del (p.Gln353SerfsTer39) variant in GAA is a frameshift variant predicted to cause a premature stop codon and to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). One patient with this variant displayed clinical features consistent with infantile-onset Pompe disease and was treated with enzyme replacement therapy (PP4_Moderate)(PMID: 29181627). This individual is compound heterozygous for the variant and a pathogenic variant, c.1057del, phase unconfirmed (PM3_Supporting)(PMID 29181627). The variant is absent from gnomAD v2.1.1 (PM2_Supporting). There is no ClinVar entry for this variant. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria met, as specified by the ClinGen LSD VCEP (Specification Version 2.0): PVS1, PP4_Moderate, PM2_Supporting, PM3_Supporting. (Classification approved on August 17th, 2021) |