ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2242G>T (p.Glu748Ter)

dbSNP: rs1057516363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000411214 SCV001371715 pathogenic Glycogen storage disease, type II 2023-04-11 reviewed by expert panel curation The NM_000152.5:c.2242G>T (p.Glu748Ter) variant in GAA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 16/20, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). One patient with this variant, diagnosed with late onset Pompe disease, has been reported (PMID: 31545528). This individual is compound heterozygous for the variant and a pathogenic variant in GAA, c.-32-13T>G, phase unknown (PMID: 31545528) (PM3_Supporting). The data are insufficient to apply PP4 based on the specifications of the ClinGen Lysosomal Diseases VCEP. The variant is absent in gnomAD v2.1.1. (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID 370268). In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): PVS1, PM3_Supporting, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP, April 11, 2023).
Counsyl RCV000411214 SCV000485530 likely pathogenic Glycogen storage disease, type II 2015-12-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV000411214 SCV004197888 pathogenic Glycogen storage disease, type II 2022-10-24 criteria provided, single submitter clinical testing

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