ClinVar Genomic variation as it relates to human health
NM_000202.8(IDS):c.1165C>T (p.Gln389Ter)
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.1165C>T (p.Gln389Ter)
Variation ID: 2138747 Accession: VCV002138747.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 149486940 (GRCh38) [ NCBI UCSC ] X: 148568471 (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 8, 2023 Aug 4, 2024 Jun 7, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000202.8:c.1165C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000193.1:p.Gln389Ter nonsense NM_001166550.4:c.895C>T NP_001160022.1:p.Gln299Ter nonsense NC_000023.11:g.149486940G>A NC_000023.10:g.148568471G>A NG_011900.3:g.23395C>T NG_042264.2:g.296G>A - Protein change
- Q389*, Q299*
- Other names
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- Canonical SPDI
- NC_000023.11:149486939: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.
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- Links
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 |
661 | 1576 | |
LOC106050102 | - | - | - | GRCh38 | - | 748 |
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
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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
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Jun 7, 2024 | RCV003050662.4 |
Submissions - Germline
Classification
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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 01, 2022)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003445270.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This variant disrupts a region of the IDS protein in which other variant(s) (p.Gln531*) have been determined to be pathogenic (PMID: 7581397, 17091340). This suggests … (more)
This variant disrupts a region of the IDS protein in which other variant(s) (p.Gln531*) have been determined to be pathogenic (PMID: 7581397, 17091340). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This premature translational stop signal has been observed in individuals with IDS-related conditions (PMID: 7887413, 32005694, 33075783). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln389*) in the IDS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 162 amino acid(s) of the IDS protein. (less)
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Pathogenic
(Jun 07, 2024)
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criteria provided, single submitter
Method: literature only
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Mucopolysaccharidosis, MPS-II
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova
Accession: SCV005089455.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024
Comment:
Classification method: ACMG Guidelines [PMID:25741868] with modifications
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Comment:
Null variant (PVS1_Strong), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Moderate), Absent from controls (or at low frequency) in gnomAD … (more)
Null variant (PVS1_Strong), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate) (less)
Number of individuals with the variant: 11
Sex: male
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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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Clinical characteristics and genotypes of 201 patients with mucopolysaccharidosis type II in China: A retrospective, observational study. | Zhong L | Clinical genetics | 2023 | PMID: 36945845 |
Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome. | Josahkian JA | American journal of medical genetics. Part C, Seminars in medical genetics | 2021 | PMID: 33960103 |
Clinical exome sequencing as the first-tier test for diagnosing developmental disorders covering both CNV and SNV: a Chinese cohort. | Dong X | Journal of medical genetics | 2020 | PMID: 32005694 |
Novel IDS Variants Identified in Three Unrelated Pakistani Patients Affected with Mucopolysaccharidosis Type II (Hunter Syndrome). | Zubaida B | Human heredity | 2019 | PMID: 33075783 |
Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients. | Brusius-Facchin AC | Molecular genetics and metabolism | 2014 | PMID: 24125893 |
Molecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient. | Lau KC | Clinica chimica acta; international journal of clinical chemistry | 2008 | PMID: 18331837 |
Effect of Hunter disease (mucopolysaccharidosis type II) mutations on molecular phenotypes of iduronate-2-sulfatase: enzymatic activity, protein processing and structural analysis. | Sukegawa-Hayasaka K | Journal of inherited metabolic disease | 2006 | PMID: 17091340 |
Molecular analysis of 40 Italian patients with mucopolysaccharidosis type II: New mutations in the iduronate-2-sulfatase (IDS) gene. | Filocamo M | Human mutation | 2001 | PMID: 11462244 |
Mucopolysaccharidosis type II: identification of six novel mutations in Italian patients. | Villani GR | Human mutation | 1997 | PMID: 9222763 |
Two new nonsense mutations (Q80X; Q389X) in patients with severe Hunter syndrome (mucopolysaccharidosis type II.). | Carrozzo R | Human mutation | 1996 | PMID: 8829647 |
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 | American journal of human genetics | 1995 | PMID: 7887413 |
Mucopolysaccharidosis type II (Hunter disease): identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients. | Sukegawa K | Human mutation | 1995 | PMID: 7581397 |
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Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.