Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001265223 | SCV001443299 | pathogenic | Glycogen storage disease, type II | 2020-06-16 | reviewed by expert panel | curation | This variant, c.763C>T (p.Gln255Ter), is a nonsense variant that is predicted to result in nonsense medicated decay and lack of gene product, meeting PVS1. The variant is absent in gnomAD v2.1.1, meeting PM2. It has been reported in trans with c.670C>T (p.Arg224Trp) in an individual with infantile-onset Pompe disease who meets the ClinGen LSD VCEP's specifications for PP4 (PMID 25026126). The in trans data from this patient was used in the assessment of p.Arg224Trp, and was not included here in order to avoid circular logic. It was also found in a heterozygote, identified by newborn screening (PMID 23430949). 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 criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PP4. |