ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.710C>T (p.Ala237Val) (rs121907944)

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
Counsyl RCV000664615 SCV000788610 uncertain significance Glycogen storage disease, type II 2017-04-28 criteria provided, single submitter clinical testing
OMIM RCV000004250 SCV000024416 pathogenic Glycogen storage disease II, adult form 2005-01-25 no assertion criteria provided literature only
Broad Institute Rare Disease Group,Broad Institute RCV000664615 SCV001422612 uncertain significance Glycogen storage disease, type II 2020-01-22 no assertion criteria provided curation The heterozygous p.Ala237Val variant in GAA has been reported in 1 German individual with Glycogen Storage Disease II (PMID: 15668445), and has also been reported as a VUS by Counsyl and pathogenic by OMIM in ClinVar (Variation ID: 4035). This variant has been identified in 0.013% (4/30616) of South Asian chromosomes and 0.001% (1/113342) European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121907944). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. The presence of this variant in combination with a reported pathogenic variant and in an individual with Glycogen Storage Disease II increases the likelihood that the p.Ala237Val variant is pathogenic (PMID: 15668445). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM3_Supporting, PM2, PP4 (Richards 2015).

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.