ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.766_767insC (p.Tyr256fs)

dbSNP: rs1555599637
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000664743 SCV001443306 likely pathogenic Glycogen storage disease, type II 2023-05-26 reviewed by expert panel curation The NM_000152.5:c.766_767insC (p.Tyr256SerfsTer74) variant in GAA is a frameshift variant that is 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). This variant is not in gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in a patient with Pompe disease in the literature, and results of functional studies are not available. There is a ClinVar entry for this variant (Variation ID: 550104. In summary, this variant meets the criteria to be classified as likely pathogenic for Pompe disease. 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 ) GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): PVS1, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP on May 26, 2023).
Counsyl RCV000664743 SCV000788751 likely pathogenic Glycogen storage disease, type II 2016-12-29 criteria provided, single submitter clinical testing

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