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  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data


Variant: NM_000203.5(IDUA):c.1029C>A (p.Tyr343Ter)

CA356984

222997 (ClinVar)

Gene: IDUA
Condition: mucopolysaccharidosis type 1
Inheritance Mode: Autosomal recessive inheritance
UUID: 8b79bc20-229b-4f3b-95ed-e2ba1b38c857
Approved on: 2024-12-05
Published on: 2025-03-03

HGVS expressions

NM_000203.5:c.1029C>A
NM_000203.5(IDUA):c.1029C>A (p.Tyr343Ter)
NC_000004.12:g.1002325C>A
CM000666.2:g.1002325C>A
NC_000004.11:g.996113C>A
CM000666.1:g.996113C>A
NC_000004.10:g.986113C>A
NG_008103.1:g.20329C>A
ENST00000247933.9:c.1029C>A
ENST00000514224.2:c.1029C>A
ENST00000652070.1:n.1085C>A
ENST00000247933.8:c.1029C>A
ENST00000514224.1:c.633C>A
ENST00000514698.5:n.1136C>A
NM_000203.4:c.1029C>A
NR_110313.1:n.1117C>A
NM_001363576.1:c.633C>A
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Pathogenic

Met criteria codes 4
PM2_Supporting PP4 PVS1 PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Lysosomal Diseases Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for IDUA Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Lysosomal Diseases VCEP
The NM_000203.5:c.1029C>A (p.Tyr343Ter) variant in IDUA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant exon 8 out of 14, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). At least 1 patient with this variant had documented IDUA deficiency within the affected range in leukocytes and urinary GAGs expressed as heparan and dermatan sulfate GAG elevation above normal range (PP4; PMID: 35141277). This variant has been detected in at least 2 individuals with MPS I. Of those individuals, both were compound heterozygous for the variant and a pathogenic variant (c.208C>T p (Gln70Ter)) and neither of those were confirmed in trans (PM3; PMID: 35141277). This variant is absent in gnomAD v4.1.0. (PM2_Supporting). To our knowledge, the results of functional assays have not been reported for this variant. In summary, this variant meets the criteria to be classified as pathogenic for MPS I based on the IDUA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert panel (Specifications Version 1.0): PVS1, PP4, PM3, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on December 5, 2024)
Met criteria codes
PM2_Supporting
This variant is absent in gnomAD v4.0 (PM2_Supporting).
PP4
At least 1 patient with this variant had documented IDUA deficiency within the affected range in leukocytes and urinary GAGs expressed as heparan and dermatan sulfate GAG elevation above normal range (PP4; PMID: 35141277).
PVS1
The NM_000203.5:c.1029C>A (p.Tyr343Ter) variant in IDUA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant exon 8 out of 14, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
PM3
This variant has been detected in at least 2 individuals with MPS I. Of those individuals, both were compound heterozygous for the variant and a pathogenic variant (c.208C>T p.(Gln70Ter)) and neither of those were confirmed in trans (PM3= 1 point; PM3; PMID: 35141277).
Curation History
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