Submissions for variant NM_000170.3(GLDC):c.2380G>A (p.Ala794Thr)

gnomAD frequency: 0.00728  dbSNP: rs141933811

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243892	SCV000302843	benign	not specified		criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000515011	SCV000610579	likely benign	not provided	2017-05-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079808	SCV000636384	benign	Glycine encephalopathy	2025-01-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000515011	SCV000842222	benign	not provided	2018-03-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000515011	SCV001155600	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	GLDC: BS2
Illumina Laboratory Services, Illumina	RCV001079808	SCV001328172	benign	Glycine encephalopathy	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000243892	SCV001482255	benign	not specified	2021-02-22	criteria provided, single submitter	clinical testing	Variant summary: GLDC c.2380G>A (p.Ala794Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0069 in 251474 control chromosomes, predominantly at a frequency of 0.009 within the Non-Finnish European subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2.9 fold of the estimated maximal expected allele frequency for a pathogenic variant in GLDC causing Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) phenotype (0.0031), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. No occurrence of c.2380G>A in individuals affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) and no experimental evidence demonstrating its impact on protein function was ascertained in the context of this evaluation. Five 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 (n=3)/likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000515011	SCV001892938	benign	not provided	2018-09-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001079808	SCV002802142	likely benign	Glycine encephalopathy	2021-10-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000515011	SCV005225334	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000515011	SCV001932093	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000243892	SCV001971226	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001079808	SCV002075731	benign	Glycine encephalopathy	2019-12-04	no assertion criteria provided	clinical testing