ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2662G>T (p.Glu888Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701656 SCV000830468 pathogenic Glycogen storage disease, type II 2018-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu888*) in the GAA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs765718882, ExAC 0.02%). This variant has been reported as homozygous, or with a second variant, in several individuals affected with glycogen storage disease, type II (GSDII), also known as Pompe disease (PMID: 17723315, 16531044, 28394184, 21644219, 28032299, 18458862, 20080426). Loss-of-function variants in GAA are known to be pathogenic (PMID: 2252923, 18425781, 22252923). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000701656 SCV000919385 pathogenic Glycogen storage disease, type II 2018-12-20 criteria provided, single submitter clinical testing Variant summary: GAA c.2662G>T (p.Glu888X) 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. The variant allele was found at a frequency of 2e-05 in 245054 control chromosomes (gnomAD). The variant, c.2662G>T, has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) in both compound heterozygotes and homozygotes (Kostera-Pruszczyk_2006, Liu_2014, Chen_2017), and is one of the most common disease variant in Northern Chinese. These data indicate that the variant is likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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