Submissions for variant NM_000203.5(IDUA):c.299+6C>T

gnomAD frequency: 0.00924  dbSNP: rs147498923

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078390	SCV000110236	benign	not specified	2014-03-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078390	SCV000302974	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000308359	SCV000451737	benign	Mucopolysaccharidosis type 1	2018-03-06	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Mendelics	RCV000987389	SCV001136676	benign	Hurler syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000078390	SCV001362837	benign	not specified	2019-07-29	criteria provided, single submitter	clinical testing	Variant summary: IDUA c.299+6C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.01 in 172956 control chromosomes in the gnomAD database, including 20 homozygotes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in IDUA causing Mucopolysaccharidosis Type 1 phenotype (0.0027), strongly suggesting that the variant is benign. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000308359	SCV001728045	benign	Mucopolysaccharidosis type 1	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000675599	SCV001949512	benign	not provided	2020-03-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22976768, 19839758, 27884173, 27238910)
Fulgent Genetics, Fulgent Genetics	RCV002490675	SCV002802547	benign	Calcium oxalate urolithiasis	2022-04-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000675599	SCV004147438	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	IDUA: BP4, BS1, BS2; SLC26A1: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000675599	SCV005306354	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675599	SCV000801294	likely benign	not provided	2018-01-05	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000078390	SCV001742087	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000675599	SCV001798032	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078390	SCV001933005	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000078390	SCV001972347	benign	not specified		no assertion criteria provided	clinical testing