Submissions for variant NM_000152.5(GAA):c.1482A>G (p.Thr494=)

gnomAD frequency: 0.00009  dbSNP: rs202064115

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725799	SCV000339488	uncertain significance	not provided	2016-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000389259	SCV000525806	likely benign	not specified	2016-12-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001087762	SCV000626516	likely benign	Glycogen storage disease, type II	2024-01-28	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001087762	SCV001422769	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The c.1482A>G (p.Thr494=) 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: 286163). This variant has been identified in 0.011% (4/35432) of Latino chromosomes and 0.011% (14/128952) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs202064115). 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	RCV001087762	SCV001810608	likely benign	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002392803	SCV002700413	likely benign	Cardiovascular phenotype	2020-09-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
CeGaT Center for Human Genetics Tuebingen	RCV000725799	SCV003917979	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	GAA: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003967751	SCV004786090	likely benign	GAA-related condition	2022-05-27	criteria provided, single submitter	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).
Natera, Inc.	RCV001087762	SCV001453428	likely benign	Glycogen storage disease, type II	2019-11-11	no assertion criteria provided	clinical testing