Submissions for variant NM_000152.5(GAA):c.2338G>A (p.Val780Ile)

gnomAD frequency: 0.71839  dbSNP: rs1126690

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000336875	SCV001371701	benign	Glycogen storage disease, type II	2020-01-23	reviewed by expert panel	curation	The highest continental population minor allele frequency for c.2338G>A (p.Val780Ile) in gnomAD v2.1.1 is 0.8129 in the South Asian population. This is higher than the ClinGen LSD VCEP's BA1 threshold (>0.01), therefore meeting the BA1 criterion. There is a ClinVar entry for this variant (Variation ID: 92476; 2 star review status) with six submitters classifying the variant as benign. In summary, this variant meets the criteria to be classified as benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: BA1.
Eurofins Ntd Llc (ga)	RCV000078171	SCV000110009	benign	not specified	2018-09-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000078171	SCV000151255	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078171	SCV000302678	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000336875	SCV000407298	benign	Glycogen storage disease, type II	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000336875	SCV001717259	benign	Glycogen storage disease, type II	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000336875	SCV001737956	benign	Glycogen storage disease, type II	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000675244	SCV001895126	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444547	SCV002732538	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.
Breakthrough Genomics, Breakthrough Genomics	RCV000675244	SCV005248763	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000336875	SCV000733736	benign	Glycogen storage disease, type II		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675244	SCV000800891	benign	not provided	2015-10-19	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000675244	SCV001552463	uncertain significance	not provided		no assertion criteria provided	clinical testing	multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 81.682% in ExAC) based on the frequency threshold of 2.76% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.7 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078171	SCV001927584	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078171	SCV001951600	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000336875	SCV002092129	benign	Glycogen storage disease, type II	2019-11-18	no assertion criteria provided	clinical testing