Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000665233 | SCV002032120 | likely pathogenic | Glycogen storage disease, type II | 2021-08-27 | reviewed by expert panel | curation | The NM_000152.5:c.2617dup (p.Tyr873LeufsTer11) variant in GAA is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 19/20. Although the premature stop codon is thought to occur in the penultimate exon of the gene, it is not within the last 50 base pairs of the exon and, therefore, it is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in patients with Pompe disease. There is a ClinVar entry for this variant (Variation ID: 550478, one star review status) with one submitter classifying the variant as likely pathogenic. This variant meets the criteria to be classified as likely pathogenic for Pompe disease based on the recommendations of the ClinGen Sequence Variant Interpretation Working Group (https://clinicalgenome.org/site/assets/files/5182/pm2_-_svi_recommendation_-_approved_sept2020.pdf). ACMG/AMP criteria met, as specified by the ClinGen Lysosomal Storage Disorders Expert Panel (Specification Version 2.0): PVS1, PM2_Supporting |
Counsyl | RCV000665233 | SCV000789318 | likely pathogenic | Glycogen storage disease, type II | 2017-01-25 | criteria provided, single submitter | clinical testing |