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NM_000202.8(IDS):c.551G>T (p.Cys184Phe) AND Mucopolysaccharidosis, MPS-II

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jun 7, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003509089.3

Allele description [Variation Report for NM_000202.8(IDS):c.551G>T (p.Cys184Phe)]

NM_000202.8(IDS):c.551G>T (p.Cys184Phe)

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.551G>T (p.Cys184Phe)
HGVS:
  • NC_000023.11:g.149498264C>A
  • NG_011900.3:g.12071G>T
  • NG_042264.2:g.11620C>A
  • NM_000202.8:c.551G>TMANE SELECT
  • NM_001166550.4:c.281G>T
  • NM_006123.5:c.551G>T
  • NP_000193.1:p.Cys184Phe
  • NP_001160022.1:p.Cys94Phe
  • NP_006114.1:p.Cys184Phe
  • NC_000023.10:g.148579795C>A
  • NR_104128.2:n.720G>T
Protein change:
C184F
Molecular consequence:
  • NM_000202.8:c.551G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166550.4:c.281G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006123.5:c.551G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104128.2:n.720G>T - 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
SCV004299018Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Oct 21, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005089122Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jun 7, 2024)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes3not providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Molecular diagnosis of 65 families with mucopolysaccharidosis type II (Hunter syndrome) characterized by 16 novel mutations in the IDS gene: Genetic, pathological, and structural studies on iduronate-2-sulfatase.

Kosuga M, Mashima R, Hirakiyama A, Fuji N, Kumagai T, Seo JH, Nikaido M, Saito S, Ohno K, Sakuraba H, Okuyama T.

Mol Genet Metab. 2016 Jul;118(3):190-197. doi: 10.1016/j.ymgme.2016.05.003. Epub 2016 May 7.

PubMed [citation]
PMID:
27246110
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004299018.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDS protein function. This missense change has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 8940265, 33676511). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 184 of the IDS protein (p.Cys184Phe).

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

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV005089122.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedliterature only PubMed (4)

Description

Located in a mutational hot spot and/or critical functional domain (PM1_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Strong)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided3not providednot providednot provided

Last Updated: Sep 29, 2024