ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2161dup (p.Glu721fs)

dbSNP: rs1555601802
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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 RCV000664981 SCV002032113 likely pathogenic Glycogen storage disease, type II 2021-08-31 reviewed by expert panel curation The c.2161dupG (p.Glu721GlyfsTer16) variant in GAA is a frameshift 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). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). One individual with this variant and Pompe disease has been reported in the literature, but the residual GAA activity and second variant were not provided and therefore PP4 cannot be assessed (PMID: 18425781). Another individual with "p.E721Rfs", identified by newborn screening had been reported (PMIDs 28196920, 29095812) but the cDNA change was not provided. There is a ClinVar entry for this variant (Variation ID: 550277; 1 star review status) with one submitter classifying the variant as likely pathogenic. This variant meets the criteria to be classified as Likely Pathogenic for Pompe disease based on the recommendations of the ClinGen Sequence Variant Interpretation Working Group (https://clinicalgenome.org/site/assets/files/5182/pm2_-_svi_recommendation_-_approved_sept2020.pdf). ACMG/AMP criteria met, as specified by the ClinGen Lysosomal Storage Disorders Expert Panel (Specification Version 2.0): PVS1, PM2_Supporting
Counsyl RCV000664981 SCV000789028 likely pathogenic Glycogen storage disease, type II 2016-12-27 criteria provided, single submitter clinical testing

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