Submissions for variant NM_000202.8(IDS):c.514C>T (p.Arg172Ter)

dbSNP: rs104894860

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000011236	SCV000628123	pathogenic	Mucopolysaccharidosis, MPS-II	2023-04-01	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 10490). This premature translational stop signal has been observed in individuals with mucopolysaccharidosis type II (PMID: 1639384, 7887413, 21829674, 24780617). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg172*) in the IDS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IDS are known to be pathogenic (PMID: 8940265, 9875019).
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	RCV000011236	SCV001480205	pathogenic	Mucopolysaccharidosis, MPS-II		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000011236	SCV002014478	pathogenic	Mucopolysaccharidosis, MPS-II	2021-09-05	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000011236	SCV002512754	pathogenic	Mucopolysaccharidosis, MPS-II	2021-07-13	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 moderate, PM2 moderate
Ambry Genetics	RCV002336081	SCV002644813	pathogenic	Inborn genetic diseases	2014-07-18	criteria provided, single submitter	clinical testing	The p.R172* pathogenic mutation (also known as c.514C>T and 638C>T), located in coding exon 5 of the IDS gene, results from a C to T substitution at nucleotide position 514. This changes the amino acid from an arginine to a stop codon within coding exon 5. This mutation was originally reported in a patient with a clinical diagnosis Hunter syndrome (Flomen RH et al. Genomics. 1992;13(3):543-550). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000011236	SCV002822851	pathogenic	Mucopolysaccharidosis, MPS-II	2023-01-16	criteria provided, single submitter	clinical testing	A Hemizygous missense variation in exon 5 of the IDS gene that results in the termination of amino acid chain at codon 172 was detected. The observed variant c.514C>T (p.Arg172Ter) has not been reported in the 1000 genomes and gnomAD databases. The in silico prediction of the variant are possibly damaging by CADD and MutationTaster2. In summary, the variant meets our criteria to be classified as pathogenic.
GeneDx	RCV002512967	SCV003194806	pathogenic	not provided	2023-01-18	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35144014, 25525159, 33676511, 21829674, 7887413, 9875019, 1639384, 30639582, 28077157)
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000011236	SCV005089115	pathogenic	Mucopolysaccharidosis, MPS-II	2024-06-07	criteria provided, single submitter	literature only	Null variant (PVS1_VeryStrong), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Strong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)
OMIM	RCV000011236	SCV000031463	pathogenic	Mucopolysaccharidosis, MPS-II	1992-07-01	no assertion criteria provided	literature only
Pediatrics, All India Institute of Medical Sciences, New Delhi	RCV000011236	SCV001573781	affects	Mucopolysaccharidosis, MPS-II	2014-04-04	no assertion criteria provided	research	The change c.514C>T (p.R172*) was found to be a nonsense variant, where the basic polar amino acid Arginine at 172 position was substituted by stop codon leading to early truncation of the peptide. It was found in the hemizygous condition in two non-familial patients with sever MPS-II phenotype. The patients hails from the Delhi and Bihar, India.