Submissions for variant NM_000152.3(GAA):c.2065G>A (p.Glu689Lys)

gnomAD frequency: 0.04051  dbSNP: rs1800309

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078165	SCV000110003	benign	not specified	2012-09-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078165	SCV000302673	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000383641	SCV000407290	benign	Glycogen storage disease, type II	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Phosphorus, Inc.	RCV000383641	SCV000679831	benign	Glycogen storage disease, type II	2017-08-01	criteria provided, single submitter	clinical testing
Invitae	RCV000383641	SCV000752099	other	Glycogen storage disease, type II	2019-01-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000383641	SCV001158934	benign	Glycogen storage disease, type II	2023-11-29	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000383641	SCV001422940	benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The p.Glu689Lys variant in GAA has been reported as a benign and likely benign variant for Glycogen Storage Disease II in ClinVar (Variation ID: 4030). This variant has been identified in 5.490% (13805/251476) of chromosomes, including 757 homozygotes, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs1800309). This variant has been seen in the general population at a frequency high enough to rule out a pathogenic role. It is a known pseudodeficiency allele that causes false-positive results in GAA deficiency enzyme assays (PMID: 20080426, 18301443). In summary, this variant meets criteria to be classified as benign for Glycogen Storage Disease II in an autosomal recessive manner based on its frequency in the general population. ACMG/AMP Criteria applied: BA1 (Richards 2015).
Genome-Nilou Lab	RCV000383641	SCV001738047	benign	Glycogen storage disease, type II	2021-06-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002415397	SCV002725156	benign	Cardiovascular phenotype	2018-12-11	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Baylor Genetics	RCV000383641	SCV004197918	pathogenic	Glycogen storage disease, type II	2021-12-06	criteria provided, single submitter	clinical testing
OMIM	RCV000004245	SCV000024411	pathogenic	Acid alpha-glucosidase, allele 4	1996-09-01	no assertion criteria provided	literature only
Genetic Services Laboratory, University of Chicago	RCV000078165	SCV000151253	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Laboratories, Mayo Clinic	RCV000675237	SCV000800883	benign	not provided	2015-12-16	no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV000675237	SCV001749932	not provided	not provided		no assertion provided	phenotyping only	Variant reported in multiple Invitae PIN participants. Variant interpreted as Benign (Pseudo deficiency allele) most recently on 9/29/2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078165	SCV001928177	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000078165	SCV001972654	benign	not specified		no assertion criteria provided	clinical testing