Submissions for variant NM_000152.5(GAA):c.1356C>T (p.Ala452=)

gnomAD frequency: 0.00006  dbSNP: rs757893858

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725823	SCV000339627	uncertain significance	not provided	2016-02-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000725823	SCV000717256	likely benign	not provided	2019-06-19	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000725823	SCV000927550	uncertain significance	not provided	2018-02-27	criteria provided, single submitter	clinical testing
Invitae	RCV001001227	SCV001043667	likely benign	Glycogen storage disease, type II	2024-01-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001227	SCV001158390	likely benign	Glycogen storage disease, type II	2019-05-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001001227	SCV001282567	uncertain significance	Glycogen storage disease, type II	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001001227	SCV001422896	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The c.1356C>T (p.Ala452=) 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 Blueprint Genetics and likely benign by GeneDx in ClinVar (Variation ID: 286268). This variant has been identified in 0.014% (5/35404) of Latino chromosomes and 0.010% (13/128368) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs757893858). 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	RCV001001227	SCV001810598	uncertain significance	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002379136	SCV002690233	likely benign	Cardiovascular phenotype	2022-02-16	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	RCV000725823	SCV004144437	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	GAA: BP4, BP7
Natera, Inc.	RCV001001227	SCV001453426	uncertain significance	Glycogen storage disease, type II	2020-01-24	no assertion criteria provided	clinical testing