NM_000202.8(IDS):c.143G>C (p.Arg48Pro) AND Mucopolysaccharidosis, MPS-II

Clinical significance:Likely pathogenic (Last evaluated: Mar 30, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000780348.1

Allele description [Variation Report for NM_000202.8(IDS):c.143G>C (p.Arg48Pro)]

NM_000202.8(IDS):c.143G>C (p.Arg48Pro)

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.143G>C (p.Arg48Pro)
HGVS:
  • NC_000023.11:g.149504254C>G
  • NG_011900.3:g.6081G>C
  • NM_000202.8:c.143G>CMANE SELECT
  • NM_001166550.4:c.-84G>C
  • NM_006123.5:c.143G>C
  • NP_000193.1:p.Arg48Pro
  • NP_006114.1:p.Arg48Pro
  • NC_000023.10:g.148585784C>G
  • NM_000202.5:c.143G>C
  • NR_104128.2:n.312G>C
Protein change:
R48P
Links:
dbSNP: rs1569560528
NCBI 1000 Genomes Browser:
rs1569560528
Molecular consequence:
  • NM_001166550.4:c.-84G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000202.8:c.143G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006123.5:c.143G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104128.2:n.312G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000917536Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Mar 30, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

Sukegawa K, Nakamura H, Kato Z, Tomatsu S, MontaƱo AM, Fukao T, Toietta G, Tortora P, Orii T, Kondo N.

Hum Mol Genet. 2000 May 22;9(9):1283-90.

PubMed [citation]
PMID:
10814710

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917536.1

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

Description

Variant summary: IDS c.143G>C (p.Arg48Pro) results in a non-conservative amino acid change in the Sulfatase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 65161 control chromosomes. The c.143G>C has been reported in the literature in an individual presented with a mild form of Mucopolysaccharidosis Type II (Hunter Syndrome) (Isogai_1998, Sukegawa_1995). At least one publication reports experimental evidence evaluating an impact on protein function. The R48P failed to be processed to mature form leading to residual activity 0.22.4% of the wild-type IDS activity in patient's fibroblasts (Sukegava_1995; Sukegawa-Hasayaka_2006). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Nov 20, 2021

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