Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000631063 | SCV001443315 | likely pathogenic | Glycogen storage disease, type II | 2023-03-10 | reviewed by expert panel | curation | The NM_000152.5:c.342del (p.Lys114AsnfsTer28) variant in GAA is a frameshift variant predicted to cause a premature stop codon, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). 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. There is a ClinVar entry for this variant (Variation ID: 526523). The classification of this variant has been upgraded from Variant of Uncertain Significance to Likely Pathogenic based on the recommendations of the ClinGen Sequence Variant Interpretation Working Group, that a variant meeting PVS1 and PM2_Supporting is classified as Likely Pathogenic (https://clinicalgenome.org/site/assets/files/5182/pm2_-_svi_recommendation_-_approved_sept2020.pdf ). In summary, this variant meets the criteria to be classified as Likely Pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria met, based on the specifications of the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): PVS1, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP, March 10, 2023). |
| Labcorp Genetics |
RCV000631063 | SCV000752053 | pathogenic | Glycogen storage disease, type II | 2021-05-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GAA are known to be pathogenic (PMID: 2252923, 18425781, 22252923). This variant has not been reported in the literature in individuals with GAA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys114Asnfs*28) in the GAA gene. It is expected to result in an absent or disrupted protein product. |
| Baylor Genetics | RCV000631063 | SCV005058755 | likely pathogenic | Glycogen storage disease, type II | 2024-01-20 | criteria provided, single submitter | clinical testing |