Submissions for variant NM_000152.5(GAA):c.693-4G>T

gnomAD frequency: 0.00019  dbSNP: rs200088236

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723555	SCV000331313	uncertain significance	not provided	2018-07-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000723555	SCV000519101	likely benign	not provided	2021-02-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29149851)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079986	SCV000626628	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	RCV001079986	SCV001422889	likely benign	Glycogen storage disease, type II	2020-01-22	criteria provided, single submitter	curation	The c.693-4G>T variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported in 1 European individual with unexplained limb-girdle muscle weakness (PMID: 29149851). This variant has also been reported as a VUS by EGL Genetic Diagnostics and a likely benign variant by GeneDx and Invitae in ClinVar (Variation ID: 281097). This variant has been identified in 0.133% (47/35422) of Latino chromosomes and 0.088% (27/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200088236). 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 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: BP4, BP7 (Richards 2015).
Baylor Genetics	RCV001079986	SCV001528210	uncertain significance	Glycogen storage disease, type II	2018-11-08	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab	RCV001079986	SCV001810373	likely benign	Glycogen storage disease, type II	2021-07-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000723555	SCV004033594	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	GAA: BP4
Natera, Inc.	RCV001079986	SCV002091952	likely benign	Glycogen storage disease, type II	2020-07-22	no assertion criteria provided	clinical testing