Submissions for variant NM_000152.5(GAA):c.2800-11C>G

gnomAD frequency: 0.00006  dbSNP: rs374571499

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000365905	SCV000407307	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000422518	SCV000522821	likely benign	not specified	2016-02-08	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.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000365905	SCV001422890	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The c.2800-11C>G variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported as a VUS by Illumina and a likely benign variant by GeneDx in ClinVar (Variation ID: 325796). This variant has been identified in 0.090% (32/35428) of Latino chromosomes, including 1 homozygote, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs374571499). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. However, novel synonymous variants supported by computational evidence without raised suspicion for an impact are likely benign (Richards 2015). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: PM2, BP4, BP7 (Richards 2015).
Genome-Nilou Lab	RCV000365905	SCV001810206	likely benign	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000365905	SCV002339163	benign	Glycogen storage disease, type II	2024-01-29	criteria provided, single submitter	clinical testing