ClinVar Genomic variation as it relates to human health
NM_000202.8(IDS):c.1327C>T (p.Arg443Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000202.8(IDS):c.1327C>T (p.Arg443Ter)
Variation ID: 10486 Accession: VCV000010486.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 149483072 (GRCh38) [ NCBI UCSC ] X: 148564603 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 20, 2014 Jul 7, 2024 Jun 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000202.8:c.1327C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000193.1:p.Arg443Ter nonsense NM_001166550.4:c.1057C>T NP_001160022.1:p.Arg353Ter nonsense NC_000023.11:g.149483072G>A NC_000023.10:g.148564603G>A NG_011900.3:g.27263C>T - Protein change
- R443*, R353*
- Other names
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- Canonical SPDI
- NC_000023.11:149483071:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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IDS | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
420 | 1079 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jun 29, 2023 | RCV000011232.17 | |
Pathogenic (1) |
no assertion criteria provided
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Dec 8, 2020 | RCV001831559.1 | |
See cases
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Pathogenic (1) |
criteria provided, single submitter
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Dec 20, 2021 | RCV004584323.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis, MPS-II
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000940520.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 10486). This premature translational stop signal has been observed in individuals with mucopolysaccharidosis II (PMID: 1303211, 18500569, 21291454, 21829674, 27146977). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg443*) in the IDS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the IDS protein. (less)
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Pathogenic
(Dec 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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see cases
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University Hospital Muenster
Accession: SCV002577793.2
First in ClinVar: Oct 08, 2022 Last updated: Jul 07, 2024 |
Comment:
ACMG categories: PVS1,PM2,PP5
Number of individuals with the variant: 1
Clinical Features:
Abnormality of lysosomal metabolism (present)
Age: 0-9 years
Sex: male
Tissue: blood
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Pathogenic
(Dec 13, 2012)
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criteria provided, single submitter
Method: research
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Mucopolysaccharidosis, MPS-II
(X-linked inheritance)
Affected status: yes
Allele origin:
maternal
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IIFP, CONICET-UNLP
Accession: SCV000262530.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
Number of individuals with the variant: 1
Sex: male
Geographic origin: Argentina
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis, MPS-II
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
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Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences
Accession: SCV001480523.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Clinical Features:
Motor delay (present) , Macrocephaly (present) , Coarse facial features (present)
Sex: male
Ethnicity/Population group: Indian
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Pathogenic
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis, MPS-II
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002014470.1
First in ClinVar: Nov 13, 2021 Last updated: Nov 13, 2021 |
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Pathogenic
(Jan 01, 1993)
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no assertion criteria provided
Method: literature only
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MUCOPOLYSACCHARIDOSIS, TYPE II
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000031459.2
First in ClinVar: Apr 04, 2013 Last updated: Feb 20, 2014 |
Comment on evidence:
In a 12-year-old Japanese boy with Hunter syndrome (MPS2; 309900) of intermediate severity, Sukegawa et al. (1992) found a C-to-T transition at nucleotide 1327 in … (more)
In a 12-year-old Japanese boy with Hunter syndrome (MPS2; 309900) of intermediate severity, Sukegawa et al. (1992) found a C-to-T transition at nucleotide 1327 in the IDS gene which resulted in substitution of a termination codon for the normal arginine at position 443 of the peptide sequence. Although the truncated enzyme protein was synthesized, it was unstable. Bunge et al. (1992) found the same mutation in a 3-year-old male (their H20). The patient had skeletal deformities but normal psychomotor development. Froissart et al. (1993) found the same mutation in 2 patients. (less)
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Pathogenic
(May 31, 2019)
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no assertion criteria provided
Method: research
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Mucopolysaccharidosis, MPS-II
Affected status: yes
Allele origin:
de novo
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Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital
Accession: SCV001482335.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Dec 08, 2020)
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no assertion criteria provided
Method: clinical testing
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Mucopolysaccharidosis type IIIA
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002084457.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II. | Uttarilli A | Clinical genetics | 2016 | PMID: 27146977 |
Identification of 17 novel mutations in 40 Argentinean unrelated families with mucopolysaccharidosis type II (Hunter syndrome). | Amartino H | Molecular genetics and metabolism reports | 2014 | DOI: 10.1016/j.ymgmr.2014.08.006 |
Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II. | Sohn YB | Clinical genetics | 2012 | PMID: 21291454 |
Analysis of the IDS gene in 38 patients with Hunter syndrome: the c.879G>A (p.Gln293Gln) synonymous variation in a female create exonic splicing. | Zhang H | PloS one | 2011 | PMID: 21829674 |
Molecular analysis of the iduronate-2-sulfatase gene in Thai patients with Hunter syndrome. | Keeratichamroen S | Journal of inherited metabolic disease | 2008 | PMID: 18500569 |
Hunter syndrome: gene deletions and rearrangements. | Froissart R | Human mutation | 1993 | PMID: 8318991 |
Intermediate form of mucopolysaccharidosis type II (Hunter disease): a C1327 to T substitution in the iduronate sulfatase gene. | Sukegawa K | Biochemical and biophysical research communications | 1992 | PMID: 1550586 |
Mutation analysis of the iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II (Hunter syndrome). | Bunge S | Human molecular genetics | 1992 | PMID: 1303211 |
Text-mined citations for rs199422227 ...
HelpRecord last updated Jul 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.