Submissions for variant NM_000152.5(GAA):c.664G>A (p.Val222Met)

gnomAD frequency: 0.00009  dbSNP: rs374569672

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000287222	SCV000344733	benign	not specified	2016-08-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001705433	SCV000730577	likely benign	not provided	2020-09-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24627108, 29095812, 23430949, 22644586, 33202836)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000631099	SCV000752092	likely benign	Glycogen storage disease, type II	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000287222	SCV002500540	likely benign	not specified	2022-03-21	criteria provided, single submitter	clinical testing	Variant summary: GAA c.664G>A (p.Val222Met) results in a conservative amino acid change located in the Galactose mutarotase, N-terminal barrel domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00077 in 244194 control chromosomes, predominantly at a frequency of 0.0054 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.28 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Fulgent Genetics, Fulgent Genetics	RCV000631099	SCV002802799	likely benign	Glycogen storage disease, type II	2021-10-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001705433	SCV002822430	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	GAA: BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV001705433	SCV004224434	uncertain significance	not provided	2022-05-03	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000631099	SCV002091946	likely benign	Glycogen storage disease, type II	2020-02-12	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930185	SCV004744088	likely benign	GAA-related disorder	2019-03-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).