Submissions for variant NM_000152.5(GAA):c.2415G>A (p.Val805=)

gnomAD frequency: 0.00112  dbSNP: rs150536507

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724845	SCV000226557	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000390395	SCV000407299	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	RCV000724845	SCV000524470	likely benign	not provided	2021-04-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000390395	SCV000626568	likely 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	RCV000390395	SCV001422812	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The heterozygous c.2415G>A (p.Val805=) variant in GAA has been reported as a likely benign variant (by GeneDx and Invitae) and a VUS (by EGL Genetic Diagnostics and Illumina) for Glycogen Storage Disease II in ClinVar (Variation ID: 194697). This variant has been identified in 0.1495% (189/126462) of European (non-Finnish) chromosomes and 0.1387% (49/35320) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs150536507). Although this variant has been seen in the general population, its frequency is not 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, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BP7, BP4 (Richards 2015).
Genome-Nilou Lab	RCV000390395	SCV001810192	uncertain significance	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002222424	SCV002500449	likely benign	not specified	2022-03-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453612	SCV002735983	likely benign	Cardiovascular phenotype	2022-02-17	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.
CeGaT Center for Human Genetics Tuebingen	RCV000724845	SCV004010577	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	GAA: BP4, BP7
Natera, Inc.	RCV000390395	SCV001455440	uncertain significance	Glycogen storage disease, type II	2019-11-11	no assertion criteria provided	clinical testing