Submissions for variant NM_000152.5(GAA):c.1203G>A (p.Gln401=)

gnomAD frequency: 0.65453  dbSNP: rs1800304

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000344845	SCV001371712	benign	Glycogen storage disease, type II	2020-01-23	reviewed by expert panel	curation	The highest continental population minor allele frequency for c.1203G>A (p.Gln401=) in gnomAD v2.1.1 is 0.74003 in the European non-Finnish population. Note that the minor allele frequency is even higher in the Ashkenazi Jewish (0.77901) and European Finnish (0.76403) populations. These allele frequencies are higher than the ClinGen LSD VCEP's BA1 threshold (>0.01), meeting this criterion. There is a ClinVar entry for this variant (Variation ID: 92461, two star review status), with 7 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)	RCV000078155	SCV000109993	benign	not specified	2018-09-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000078155	SCV000151249	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078155	SCV000302658	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000344845	SCV000407278	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.
Phosphorus, Inc.	RCV000344845	SCV000679764	benign	Glycogen storage disease, type II	2017-08-01	criteria provided, single submitter	clinical testing
Invitae	RCV000344845	SCV001725521	benign	Glycogen storage disease, type II	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000344845	SCV001738033	benign	Glycogen storage disease, type II	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000675226	SCV001836247	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345390	SCV002648749	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000344845	SCV000733729	benign	Glycogen storage disease, type II		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675226	SCV000800872	benign	not provided	2015-10-22	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000675226	SCV001551894	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: 77.971% in gnomAD_ExomesFounderPop) 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.A synonymous variant not located in a splice region.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078155	SCV001928466	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078155	SCV001953527	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000344845	SCV002092000	benign	Glycogen storage disease, type II	2020-10-16	no assertion criteria provided	clinical testing