Submissions for variant NM_000152.5(GAA):c.858+7_858+8insAGCGGGC

dbSNP: rs3071247

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000578107	SCV001443319	benign	Glycogen storage disease, type II	2020-05-19	reviewed by expert panel	curation	The highest continental population minor allele frequency for c.858+7_858+8insAGCGGGC in gnomAD v.2.1.1 is 0.7353 in the European non-Finnish population. This allele frequency is higher than the ClinGen LSD VCEP's BA1 threshold (>0.01), meeting this criterion. Note that the minor allele frequency is even higher in the Ashkenazi Jewish (0.7783) and European Finnish (0.7613) populations. There is a ClinVar entry for this variant (Variation ID: 92489, 2 star review status), with 10 submitters all 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)	RCV000078186	SCV000110024	benign	not specified	2018-09-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000078186	SCV000247443	benign	not specified	2015-08-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078186	SCV000302699	benign	not specified		criteria provided, single submitter	clinical testing
Phosphorus, Inc.	RCV000578107	SCV000679771	benign	Glycogen storage disease, type II	2017-08-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588321	SCV000695667	benign	not provided	2017-08-21	criteria provided, single submitter	clinical testing	Variant summary: The GAA c.858+7_858+8insAGCGGGC variant involves insertion of 7 nucleotides in an intronic location, which 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 179851/270478 control chromosomes (3918 homozygotes) at a frequency of 0.6649376, which is approximately 158 times the estimated maximal expected allele frequency of a pathogenic GAA variant (0.0042205). The observed allele frequency indicates the variant of interest is the major allele observed in the general population. In addition, the region is indicated to be highly polymorphic in gnomAD. A publication cites the variant to co-occur in an affected individual that carried two pathogenic variants. Furthermore, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign.
GeneDx	RCV000588321	SCV000728468	benign	not provided	2018-06-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000578107	SCV000752093	benign	Glycogen storage disease, type II	2025-02-04	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV003993793	SCV004812369	benign	Metabolic myopathy	2023-05-04	criteria provided, single submitter	clinical testing	European Non-Finnish population allele frequency is 73.16%% (rs3071247, 161447/242952 alleles, 55293 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.1.0, this variant is classified as BENIGN. Following criteria are met: BA1
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000578107	SCV000733726	benign	Glycogen storage disease, type II		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000578107	SCV000733727	benign	Glycogen storage disease, type II		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000588321	SCV000800867	benign	not provided	2015-12-07	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000578107	SCV001453597	benign	Glycogen storage disease, type II	2020-09-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000588321	SCV001800190	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078186	SCV001958325	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000588321	SCV001964484	likely benign	not provided		no assertion criteria provided	clinical testing