ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2066_2069del (p.Glu689fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226644 SCV003922540 pathogenic Glycogen storage disease, type II 2023-03-28 criteria provided, single submitter clinical testing Variant summary: GAA c.2066_2069delAGCC (p.Glu689GlyfsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 225448 control chromosomes (gnomAD). c.2066_2069delAGCC has been reported in the literature in a homozygous individual affected with Glycogen Storage Disease (Infantile Pompe Disease) with near absent enzyme activity in dried blood spot (example: Ceron- Rodriguez_2022). These data indicate that the variant is very likely associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003226644 SCV004195504 pathogenic Glycogen storage disease, type II 2023-08-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003226644 SCV005829147 pathogenic Glycogen storage disease, type II 2024-08-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu689Glyfs*6) 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: 35532199). ClinVar contains an entry for this variant (Variation ID: 2501047). For these reasons, this variant has been classified as Pathogenic.

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