ClinVar Genomic variation as it relates to human health
NM_000202.8(IDS):c.133G>C (p.Asp45His)
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.133G>C (p.Asp45His)
Variation ID: 221970 Accession: VCV000221970.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 149504264 (GRCh38) [ NCBI UCSC ] X: 148585794 (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 12, 2016 Aug 4, 2024 Jun 7, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000202.8:c.133G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000193.1:p.Asp45His missense NM_001166550.4:c.-94G>C 5 prime UTR NM_006123.5:c.133G>C NP_006114.1:p.Asp45His missense NR_104128.2:n.302G>C non-coding transcript variant NC_000023.11:g.149504264C>G NC_000023.10:g.148585794C>G NG_011900.3:g.6071G>C - Protein change
- D45H
- Other names
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- Canonical SPDI
- NC_000023.11:149504263:C:G
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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 |
663 | 1580 |
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
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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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 7, 2024 | RCV000207419.7 |
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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Likely pathogenic
(Oct 18, 2015)
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criteria provided, single submitter
Method: research
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Mucopolysaccharidosis, MPS-II
Affected status: yes
Allele origin:
maternal
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MOLECULAR BIOLOGY LABORATORY, INSTITUTO NACIONAL DE PEDIATRIA
Accession: SCV000262703.1
First in ClinVar: Feb 12, 2016 Last updated: Feb 12, 2016
Comment:
Variation absent in 133 IDS normal alleles (MwoI restriction) from Mexican-descent healthy controls.
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Comment:
Likely pathogenic variation identified in a Hunter syndrome male patient without I2S evaluation. He presents mental retardation and seizures. No hydrocephaly. Pathogenicity clues: Highly conserved … (more)
Likely pathogenic variation identified in a Hunter syndrome male patient without I2S evaluation. He presents mental retardation and seizures. No hydrocephaly. Pathogenicity clues: Highly conserved nucleotide (phyloP: 0.86 [-5.2;1.1]); Highly conserved amino acid, up to Fruitfly (considering 12 species); Moderate physicochemical difference between Asp and His (Grantham dist.: 81 [0-215]); This variant is in protein domains: Sulfatase, Alkaline-phosphatase-like, core domain, Align GVGD: C0 (GV: 213.16 - GD: 59.84); SIFT: Deleterious (score: 0, median: 3.50); MutationTaster: disease causing (p-value: 1); Polyphen prediction: Probably Damaging (HumDiv score 1.0) (less)
Number of individuals with the variant: 1
Age: 10-19 years
Sex: male
Ethnicity/Population group: Mexican
Geographic origin: Mexico
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Pathogenic
(Jan 14, 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: SCV001576860.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp45 amino acid residue in IDS. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp45 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 9875019, 24125893), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 221970). This missense change has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 26762690; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 45 of the IDS protein (p.Asp45His). (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: SCV005089243.1
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:
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 … (more)
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) (less)
Number of individuals with the variant: 1
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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Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome. | Alcántara-Ortigoza MA | Clinical genetics | 2016 | PMID: 26762690 |
Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients. | Brusius-Facchin AC | Molecular genetics and metabolism | 2014 | PMID: 24125893 |
Mutation analysis in 57 unrelated patients with MPS II (Hunter's disease). | Vafiadaki E | Archives of disease in childhood | 1998 | PMID: 9875019 |
Text-mined citations for rs869025301 ...
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.