ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2242del (p.Glu748fs)

dbSNP: rs777275355
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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 RCV000409225 SCV002032114 pathogenic Glycogen storage disease, type II 2024-01-15 reviewed by expert panel curation The NM_000152.5:c.2242del (p.Glu748ArgfsTer16) variant in GAA is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 16 out of 20, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). One Chinese patient with late-onset Pompe disease has been described who is compound heterozygous for the variant and c.1634C>T (p.Pro545Leu). This individual has documented values showing deficiency GAA activity in dried blood spots (PMID: 35071497) (PP4_Moderate). The allelic data from this individual will be used in the classification of p.Pro545Leu and is not included here to avoid circular logic. This variant is absent in gnomAD v2.1.1. (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID 370639). This variant was initially classified by the ClinGen Lysosomal Diseases VCEP on Sept 07, 2021 as likely pathogenic. Recuration, on Jan 15, 2023, led to reclassification as pathogenic due to the availability of new case-level data (PMID: 35071497). GAA-specific ACMG/AMP criteria met, as specified by the ClinGen Lysosomal Diseases Expert Panel (Specifications Version 2.0): PVS1, PP4_Moderate, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on Jan 15, 2024).
Counsyl RCV000409225 SCV000486006 likely pathogenic Glycogen storage disease, type II 2016-03-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV000409225 SCV004195501 pathogenic Glycogen storage disease, type II 2024-03-20 criteria provided, single submitter clinical testing

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