Submissions for variant NM_000152.5(GAA):c.600C>T (p.Val200=)

gnomAD frequency: 0.00038  dbSNP: rs150895924

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000247742	SCV000302692	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000725492	SCV000337289	uncertain significance	not provided	2015-11-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087957	SCV000626618	likely benign	Glycogen storage disease, type II	2025-01-23	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001087957	SCV001422778	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The c.600C>T (p.Val200=) 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 Invitae and PreventionGenetics in ClinVar (Variation ID: 255364). This variant has been identified in 0.1205% (30/24906) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs150895924). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. 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: BP4, BP7 (Richards 2015).
GeneDx	RCV000725492	SCV001795476	likely benign	not provided	2021-04-13	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001087957	SCV001810307	likely benign	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002356340	SCV002656594	likely benign	Cardiovascular phenotype	2022-05-27	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.