ClinVar Genomic variation as it relates to human health
NM_000203.5(IDUA):c.1728-1G>C
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_000203.5(IDUA):c.1728-1G>C
Variation ID: 556064 Accession: VCV000556064.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4p16.3 4: 1004011 (GRCh38) [ NCBI UCSC ] 4: 997799 (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 Aug 5, 2018 Feb 7, 2023 Aug 10, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000203.5:c.1728-1G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001363576.1:c.1332-1G>C splice acceptor NC_000004.12:g.1004011G>C NC_000004.11:g.997799G>C NG_008103.1:g.22015G>C LRG_1277:g.22015G>C LRG_1277t1:c.1728-1G>C - Protein change
- Other names
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- Canonical SPDI
- NC_000004.12:1004010:G:C
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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.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00000
- 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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IDUA | - | - |
GRCh38 GRCh37 |
1383 | 2117 |
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 (3) |
criteria provided, single submitter
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Aug 10, 2022 | RCV001249440.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 29, 2019 | RCV001592853.10 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Nov 18, 2021 | RCV001810477.10 |
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
(Jul 29, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001822888.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant in a gene for which loss-of-function is a known mechanism of … (more)
Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28752568, 22976768) (less)
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Likely pathogenic
(Nov 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis, MPS-I-H/S
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV002060268.2
First in ClinVar: Jan 15, 2022 Last updated: Nov 29, 2022 |
Comment:
NM_000203.3(IDUA):c.1728-1G>C is a a canonical splice variant classified as likely pathogenic in the context of mucopolysaccharidosis type I. c.1728-1G>C has been observed in cases with … (more)
NM_000203.3(IDUA):c.1728-1G>C is a a canonical splice variant classified as likely pathogenic in the context of mucopolysaccharidosis type I. c.1728-1G>C has been observed in cases with relevant disease (PMID: 31194252). Functional assessments of this variant are not available in the literature. c.1728-1G>C has not been observed in population frequency databases. In summary, NM_000203.3(IDUA):c.1728-1G>C is a canonical splice variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Aug 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002219477.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change affects an acceptor splice site in intron 12 of the IDUA gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 12 of the IDUA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with mucopolysaccharidosis type I (PMID: 22976768, 28752568). ClinVar contains an entry for this variant (Variation ID: 556064). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 05, 2021)
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no assertion criteria provided
Method: clinical testing
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Mucopolysaccharidosis type I
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002075384.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Mucopolysaccharidosis type 1
Affected status: unknown
Allele origin:
maternal
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GenomeConnect, ClinGen
Accession: SCV001423448.1
First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020 |
Comment:
Variant interpretted as Pathogenic and reported on 07-30-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpretted as Pathogenic and reported on 07-30-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of the amniotic fluid (present) , Abnormal delivery (present) , Premature birth (present) , Short stature (present) , Abnormality of the chin (present) , … (more)
Abnormality of the amniotic fluid (present) , Abnormal delivery (present) , Premature birth (present) , Short stature (present) , Abnormality of the chin (present) , Abnormal facial shape (present) , Abnormality of the neck (present) , Abnormality of the skull (present) , Hypermetropia (present) , Asthma (present) , Abnormal pattern of respiration (present) , Feeding difficulties (present) , Abnormality of esophagus morphology (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Testing laboratory: GeneDx
Date variant was reported to submitter: 2019-07-30
Testing laboratory interpretation: Pathogenic
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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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Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry. | Clarke LA | Clinical genetics | 2019 | PMID: 31194252 |
IDUA mutational profile and genotype-phenotype relationships in UK patients with Mucopolysaccharidosis Type I. | Ghosh A | Human mutation | 2017 | PMID: 28752568 |
Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations. | Pollard LM | Journal of inherited metabolic disease | 2013 | PMID: 22976768 |
Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis. | Wang X | Clinical genetics | 2012 | PMID: 21480867 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. | Beesley CE | Human genetics | 2001 | PMID: 11735025 |
Text-mined citations for rs1249951282 ...
HelpRecord last updated Apr 20, 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.