Submissions for variant NM_000152.5(GAA):c.2780C>T (p.Thr927Ile)

gnomAD frequency: 0.04402  dbSNP: rs1800315

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000308857	SCV001371703	benign	Glycogen storage disease, type II	2020-01-23	reviewed by expert panel	curation	The highest continental population minor allele frequency for c.2780C>T (p.Thr927Ile) in gnomAD v2.1.1 is 0.1317 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: 92482; 2 star review status) with six 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)	RCV000078178	SCV000110016	benign	not specified	2013-08-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078178	SCV000302685	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000308857	SCV000407306	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.
GeneDx	RCV000078178	SCV000517803	benign	not specified	2015-12-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000308857	SCV000626601	benign	Glycogen storage disease, type II	2024-02-01	criteria provided, single submitter	clinical testing
Phosphorus, Inc.	RCV000308857	SCV000679768	benign	Glycogen storage disease, type II	2017-08-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002433584	SCV002751682	benign	Cardiovascular phenotype	2020-03-19	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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	RCV000078178	SCV000151259	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	RCV000675250	SCV000800897	benign	not provided	2017-05-17	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000308857	SCV001463867	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)	RCV000675250	SCV001799730	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078178	SCV001929227	benign	not specified		no assertion criteria provided	clinical testing