Submissions for variant NM_000152.5(GAA):c.547-4C>G

gnomAD frequency: 0.65665  dbSNP: rs3816256

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000369731	SCV001371709	benign	Glycogen storage disease, type II	2020-01-23	reviewed by expert panel	curation	The highest continental population minor allele frequency for c.547-4C>G in gnomAD v2.1.1 is 0.7403 in the European non-Finnish population. Note that the minor allele frequency is even higher in the Ashkenazi Jewish (0.77927) and European Finnish (0.75914) 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: 92485, two star review status), with 6 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)	RCV000078182	SCV000110020	benign	not specified	2018-09-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000078182	SCV000151262	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078182	SCV000302690	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000369731	SCV000407264	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.
Invitae	RCV000369731	SCV001725517	benign	Glycogen storage disease, type II	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000369731	SCV001738009	benign	Glycogen storage disease, type II	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000675216	SCV001851954	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345391	SCV002654317	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	RCV000369731	SCV000733722	benign	Glycogen storage disease, type II		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675216	SCV000800860	benign	not provided	2015-10-19	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000675216	SCV001552622	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: 77.996% 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.6 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	RCV000078182	SCV001926875	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078182	SCV001952123	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000369731	SCV002091934	benign	Glycogen storage disease, type II	2019-11-18	no assertion criteria provided	clinical testing