Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001265219 | SCV001443289 | likely pathogenic | Glycogen storage disease, type II | 2023-03-10 | reviewed by expert panel | curation | The NM_000152.5:c.1692del (p.Leu565SerfsTer13) 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, and the results of functional studies are not available. There is a ClinVar entry for this variant (Variation ID: 520974). 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). |
| Ambry Genetics | RCV000622656 | SCV000741349 | pathogenic | Inborn genetic diseases | 2016-02-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001265219 | SCV002228058 | pathogenic | Glycogen storage disease, type II | 2020-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu565Serfs*13) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 520974). For these reasons, this variant has been classified as Pathogenic. |