Submissions for variant NM_000152.5(GAA):c.2446G>A (p.Val816Ile)

gnomAD frequency: 0.05752  dbSNP: rs1800314

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000296830	SCV001371702	benign	Glycogen storage disease, type II	2020-01-23	reviewed by expert panel	curation	The highest continental population minor allele frequency for c.2446G>A (p.Val816Ile) in gnomAD v2.1.1 is 0.14249 in the African 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: 92477; 2 star review status) with four submitters classifying the variant as benign, and two as likely 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)	RCV000078172	SCV000110010	benign	not specified	2013-08-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078172	SCV000302680	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000296830	SCV000407300	benign	Glycogen storage disease, type II	2018-01-12	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.	RCV000296830	SCV000679767	benign	Glycogen storage disease, type II	2017-08-01	criteria provided, single submitter	clinical testing
Invitae	RCV000296830	SCV001717260	benign	Glycogen storage disease, type II	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000296830	SCV001737957	benign	Glycogen storage disease, type II	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000675246	SCV001849181	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 1684505, 25681614, 25526786, 17210890, 8486380, 8094613)
Ambry Genetics	RCV002453395	SCV002737983	benign	Cardiovascular phenotype	2019-07-24	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.
Genetic Services Laboratory, University of Chicago	RCV000078172	SCV000151256	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	RCV000675246	SCV000800893	benign	not provided	2017-05-17	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000296830	SCV002094459	benign	Glycogen storage disease, type II	2019-11-22	no assertion criteria provided	clinical testing