Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001200875 | SCV001371776 | pathogenic | Glycogen storage disease, type II | 2020-02-14 | reviewed by expert panel | curation | This variant, c.399C>A (p.Tyr133Ter), is a nonsense variant that is predicted to result in nonsense mediated decay and absence of gene product, meeting PVS1. When expressed in COS-1 cells, the variant results in no GAA activity and the mutant protein cannot be detected on Western blot, (PMID 14972326) supporting that it is a loss of function variant. The variant is absent in gnomAD v2.1.1, meeting PM2. A patient with infantile onset Pompe disease meeting the ClinGen LSD VCEP's specifications for PP4 has been reported who is homozygous for the variant; both parents were confirmed to be heterozygotes (PMID 14972326), meeting PM3_Supporting. There is no ClinVar entry for this varint. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PM3_Supporting, PP4. |