ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.545C>G (p.Thr182Arg)

dbSNP: rs200524747
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000631066 SCV001371773 uncertain significance Glycogen storage disease, type II 2023-05-26 reviewed by expert panel curation The NM_000152.5(GAA):c.545C>G (p.Thr182Arg) variant in GAA has a highest population minor allele frequency in gnomAD v2.1.1 of 0.00010 (11/106436 alleles) in the European (Non-Finnish) population, which is lower than the ClinGen LD VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). The variant has been reported in the literature but not in individuals diagnosed with Pompe disease (PMID: 29149851, 33552729) (PP4 is not met). The computational predictor REVEL gives a score of 0.395, a score which does not clearly predict an impact on GAA function (PMID: 36413997). There is a ClinVar entry for this variant (Variation ID: 499380). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP on May 26, 2023).
Eurofins Ntd Llc (ga) RCV000594745 SCV000704834 uncertain significance not provided 2017-10-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000631066 SCV000752057 uncertain significance Glycogen storage disease, type II 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 182 of the GAA protein (p.Thr182Arg). This variant is present in population databases (rs200524747, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 499380). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV000594745 SCV003834070 uncertain significance not provided 2021-12-27 criteria provided, single submitter clinical testing
GeneDx RCV000594745 SCV003837020 uncertain significance not provided 2023-02-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29149851, 22253258, 19343043)
Natera, Inc. RCV000631066 SCV002091929 uncertain significance Glycogen storage disease, type II 2020-07-17 no assertion criteria provided clinical testing

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.