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NM_000203.5(IDUA):c.1524+1G>A AND Mucopolysaccharidosis type 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 23, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001210161.6

Allele description [Variation Report for NM_000203.5(IDUA):c.1524+1G>A]

NM_000203.5(IDUA):c.1524+1G>A

Gene:
IDUA:alpha-L-iduronidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p16.3
Genomic location:
Preferred name:
NM_000203.5(IDUA):c.1524+1G>A
HGVS:
  • NC_000004.12:g.1003158G>A
  • NG_008103.1:g.21162G>A
  • NG_101700.1:g.47G>A
  • NM_000203.5:c.1524+1G>AMANE SELECT
  • NM_001363576.1:c.1128+1G>A
  • LRG_1277t1:c.1524+1G>A
  • LRG_1277:g.21162G>A
  • NC_000004.11:g.996946G>A
  • NM_000203.4:c.1524+1G>A
Links:
dbSNP: rs1553917483
NCBI 1000 Genomes Browser:
rs1553917483
Molecular consequence:
  • NM_000203.5:c.1524+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001363576.1:c.1128+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Mucopolysaccharidosis type 1
Synonyms:
Mucopolysaccharidosis type I; MPS 1; Attenuated MPS I (subtype); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0001586; MedGen: C0023786

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001381632Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Aug 23, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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, Meaney CA, Greenland G, Adams V, Vellodi A, Young EP, Winchester BG.

Hum Genet. 2001 Nov;109(5):503-11. Epub 2001 Oct 19.

PubMed [citation]
PMID:
11735025
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001381632.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with IDUA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change affects a donor splice site in intron 10 of the IDUA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024