Submissions for variant NM_000203.5(IDUA):c.346G>A (p.Gly116Arg)

gnomAD frequency: 0.00289  dbSNP: rs148946496

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000884870	SCV001028273	benign	Mucopolysaccharidosis type 1	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000884870	SCV001313833	benign	Mucopolysaccharidosis type 1	2017-04-28	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.
GeneDx	RCV001354147	SCV001758061	likely benign	not provided	2020-05-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001354147	SCV004147448	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	IDUA: BP4, BS1
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354147	SCV001548690	likely benign	not provided		no assertion criteria provided	clinical testing	The IDUA p.G116R variant was identified in one heterozygous individual with mucopolysaccharidosis type I; however, this individual was also homozygous for a frameshift variant in the same gene (Bunge_1994_PMID: 7951228). The variant was identified in dbSNP (ID: rs148946496) and ClinVar (classified as benign by Invitae and Illumina). The variant was identified in control databases in 286 of 281714 chromosomes at a frequency of 0.001015, and was observed at the highest frequency in the African population in 240 of 24866 chromosomes (freq: 0.009652) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.G116 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome, Splice AI genome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001354147	SCV001799402	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001354147	SCV001953024	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000884870	SCV002083098	likely benign	Mucopolysaccharidosis type 1	2017-05-06	no assertion criteria provided	clinical testing