ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.768dup (p.Ile257fs)

dbSNP: rs1555599644
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000672554 SCV001443308 likely pathogenic Glycogen storage disease, type II 2023-03-10 reviewed by expert panel curation The NM_000152.5:c.768dup (p.Ile257TyrfsTer73) 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). This variant is not in gnomAD v2.1.1. (PM2_Supporting). The variant has been reported in a patient with Pompe disease but further details regarding the second variant and residual GAA activity are unavailable (PMID: 18425781). There is a ClinVar entry for this variant (Variation ID: 556534). 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 RCV000672554 SCV000797667 likely pathogenic Glycogen storage disease, type II 2018-02-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000672554 SCV004296861 pathogenic Glycogen storage disease, type II 2023-02-25 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 556534). This sequence change creates a premature translational stop signal (p.Ile257Tyrfs*73) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 18425781). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.