ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.393del (p.Ser132fs)

dbSNP: rs1057517381
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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 RCV000411224 SCV001443316 likely pathogenic Glycogen storage disease, type II 2023-03-10 reviewed by expert panel curation The NM_000152.5:c.393del (p.Ser132AlafsTer10) 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: 371580). 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).
Counsyl RCV000411224 SCV000487196 likely pathogenic Glycogen storage disease, type II 2016-10-25 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000411224 SCV005653175 likely pathogenic Glycogen storage disease, type II 2024-04-18 criteria provided, single submitter clinical testing

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