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NM_000202.8(IDS):c.1123G>T (p.Glu375Ter) 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:
RCV001950793.5

Allele description [Variation Report for NM_000202.8(IDS):c.1123G>T (p.Glu375Ter)]

NM_000202.8(IDS):c.1123G>T (p.Glu375Ter)

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.1123G>T (p.Glu375Ter)
HGVS:
  • NC_000023.11:g.149486982C>A
  • NG_011900.3:g.23353G>T
  • NG_042264.2:g.338C>A
  • NM_000202.8:c.1123G>TMANE SELECT
  • NM_001166550.4:c.853G>T
  • NP_000193.1:p.Glu375Ter
  • NP_001160022.1:p.Glu285Ter
  • NC_000023.10:g.148568513C>A
  • NG_042264.1:g.337C>A
Protein change:
E285*
Links:
dbSNP: rs782634993
NCBI 1000 Genomes Browser:
rs782634993
Molecular consequence:
  • NM_000202.8:c.1123G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001166550.4:c.853G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002231468Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Aug 7, 2021)
germlineclinical testing

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

SCV005089442Laboratory 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

Mucopolysaccharidosis type II (Hunter syndrome): mutation "hot spots" in the iduronate-2-sulfatase gene.

Rathmann M, Bunge S, Beck M, Kresse H, Tylki-Szymanska A, Gal A.

Am J Hum Genet. 1996 Dec;59(6):1202-9.

PubMed [citation]
PMID:
8940265
PMCID:
PMC1914889

Mutation analysis in 57 unrelated patients with MPS II (Hunter's disease).

Vafiadaki E, Cooper A, Heptinstall LE, Hatton CE, Thornley M, Wraith JE.

Arch Dis Child. 1998 Sep;79(3):237-41.

PubMed [citation]
PMID:
9875019
PMCID:
PMC1717680
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231468.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 8111411, 30639582). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu375*) 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).

#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, SCV005089442.1

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

Description

Null variant (PVS1_VeryStrong), De novo (PS2_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_Strong)

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

Last Updated: Sep 29, 2024