Submissions for variant NM_000152.5(GAA):c.2109C>T (p.Tyr703=)

gnomAD frequency: 0.00038  dbSNP: rs150728610

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726677	SCV000345935	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082960	SCV000626544	likely benign	Glycogen storage disease, type II	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000726677	SCV000714878	likely benign	not provided	2019-10-22	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001082960	SCV001422615	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The c.2109C>T (p.Tyr703=) variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported as a VUS by EGL Genetic Diagnostics and a likely benign variant by GeneDx and Invitae in ClinVar (Variation ID: 291223). This variant has been identified in 0.094% (21/22256) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs150728610). 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 suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. However, novel synonymous variants supported by computational evidence without raised suspicion for an impact are likely benign (Richards 2015). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: PM2, BP4, BP7 (Richards 2015).
Genome-Nilou Lab	RCV001082960	SCV001810643	likely benign	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002418138	SCV002726947	likely benign	Cardiovascular phenotype	2022-03-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc.	RCV001082960	SCV001455430	uncertain significance	Glycogen storage disease, type II	2020-01-24	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003949961	SCV004762065	likely benign	GAA-related disorder	2019-11-08	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).