Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000665533 | SCV001371743 | uncertain significance | Glycogen storage disease, type II | 2023-03-13 | reviewed by expert panel | curation | The NM_000152.5:c.400_408dup variant in GAA is predicted to cause a change in the length of the protein due to an in-frame duplication of 3 amino acids in a non-repeat region (p.Pro134_Tyr136dup) (PM4). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and results of experimental studies are not available. Computational evidence is conflicting; PROVEAN predicts that the variant will impact the function of GAA, while Mutation Taster predicts no impact. No impact on splicing is predicted by SpliceAI. As a result, neither PP3 nor BP4 can be applied. There is a ClinVar entry for this variant (Variation ID: 550713). 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 VCEP: PM4, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP on March 13, 2023). |
Counsyl | RCV000665533 | SCV000789673 | uncertain significance | Glycogen storage disease, type II | 2017-02-09 | criteria provided, single submitter | clinical testing |