Submissions for variant NM_000152.5(GAA):c.2478G>A (p.Leu826=)

gnomAD frequency: 0.00031  dbSNP: rs201183207

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000395311	SCV000338813	likely benign	not specified	2016-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000335490	SCV000407301	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001534583	SCV000534360	likely benign	not provided	2021-07-09	criteria provided, single submitter	clinical testing
Invitae	RCV000335490	SCV000626576	benign	Glycogen storage disease, type II	2024-01-31	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000335490	SCV001422813	benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The p.Leu826= variant in GAA has been reported as a benign variant (by Invitae), a likely benign variant (by GeneDx and EGL), and a VUS (by Illumina) in ClinVar (Variation ID: 285676). This variant has been identified in 1.233% (238/19306) of East Asian chromosomes, including 3 homozygotes as well as other populations at lesser frequencies by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201183207). This variant has been seen in the general population at a frequency high enough to rule out a pathogenic role. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, this variant meets criteria to be classified as benign for Glycogen Storage Disease II in an autosomal recessive manner based on its frequency in the general population. ACMG/AMP Criteria applied: BA1, BP7, BP4 (Richards 2015).
Ambry Genetics	RCV002446522	SCV002735382	likely benign	Cardiovascular phenotype	2022-03-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Natera, Inc.	RCV000335490	SCV002094466	likely benign	Glycogen storage disease, type II	2019-10-24	no assertion criteria provided	clinical testing