NM_000202.8(IDS):c.514C>T (p.Arg172Ter) AND Mucopolysaccharidosis, MPS-II

Clinical significance:Pathogenic (Last evaluated: Sep 5, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000011236.12

Allele description [Variation Report for NM_000202.8(IDS):c.514C>T (p.Arg172Ter)]

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

Genes:
LOC106050102:IDS recombination region [Gene]
IDS:iduronate 2-sulfatase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000202.8(IDS):c.514C>T (p.Arg172Ter)
HGVS:
  • NC_000023.11:g.149498301G>A
  • NG_011900.3:g.12034C>T
  • NG_042264.1:g.11656G>A
  • NM_000202.8:c.514C>TMANE SELECT
  • NM_001166550.4:c.244C>T
  • NM_006123.5:c.514C>T
  • NP_000193.1:p.Arg172Ter
  • NP_001160022.1:p.Arg82Ter
  • NP_006114.1:p.Arg172Ter
  • NC_000023.10:g.148579832G>A
  • NM_000202.6:c.514C>T
  • NR_104128.2:n.683C>T
Protein change:
R172*; ARG172TER
Links:
OMIM: 300823.0005; dbSNP: rs104894860
NCBI 1000 Genomes Browser:
rs104894860
Molecular consequence:
  • NR_104128.2:n.683C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000202.8:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001166550.4:c.244C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_006123.5:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
Functional consequence:
termination codon change [Variation Ontology: 0309]
Observations:
1

Condition(s)

Name:
Mucopolysaccharidosis, MPS-II (MPS2)
Synonyms:
Mucopolysaccharidosis type II; Attenuated MPS (subtype; formerly known as mild MPS II); Severe MPS II; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010674; MedGen: C0026705; Orphanet: 580; OMIM: 309900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000031463OMIMno assertion criteria providedPathogenic
(Jul 1, 1992)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000628123Invitaecriteria provided, single submitter
Pathogenic
(Sep 12, 2017)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001480205Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciencescriteria provided, single submitter
Pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001573781Pediatrics,All India Institute of Medical Sciences, New Delhino assertion criteria providedAffects
(Apr 4, 2014)
germlineresearch

SCV002014478Nilou-Genome Labcriteria provided, single submitter
Pathogenic
(Sep 5, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
INDIANgermlineyes22not providednot providednot providedresearch
Indiangermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular diagnosis of mucopolysaccharidosis type II (Hunter syndrome) by automated sequencing and computer-assisted interpretation: toward mutation mapping of the iduronate-2-sulfatase gene.

Jonsson JJ, Aronovich EL, Braun SE, Whitley CB.

Am J Hum Genet. 1995 Mar;56(3):597-607.

PubMed [citation]
PMID:
7887413
PMCID:
PMC1801163

Genetic analysis of 17 children with Hunter syndrome: identification and functional characterization of four novel mutations in the iduronate-2-sulfatase gene.

Chistiakov DA, Kuzenkova LM, Savost'anov KV, Gevorkyan AK, Pushkov AA, Nikitin AG, Vashakmadze ND, Zhurkova NV, Podkletnova TV, Namazova-Baranova LS, Baranov AA.

J Genet Genomics. 2014 Apr 20;41(4):197-203. doi: 10.1016/j.jgg.2014.01.007. Epub 2014 Feb 4.

PubMed [citation]
PMID:
24780617
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000031463.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In their patient 2 with Hunter syndrome (309900), Flomen et al. (1992) identified a C-to-T transition at nucleotide 638 of the IDS gene, converting arginine 172 to a stop codon.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000628123.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with mucopolysaccharidosis type II (PMID: 7887413, 1639384 , 21829674, 24780617). ClinVar contains an entry for this variant (Variation ID: 10490). Loss-of-function variants in IDS are known to be pathogenic (PMID: 8940265, 9875019). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, SCV001480205.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Indian1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Pediatrics,All India Institute of Medical Sciences, New Delhi, SCV001573781.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1INDIAN2not providednot providedresearchnot provided

Description

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.

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not provided2not provided

From Nilou-Genome Lab, SCV002014478.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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