{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/b97d1371-e9cc-45bc-9b2b-fb9084c93edc/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1529725529", "label": "ClinGen Lysosomal Diseases Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for IDUA Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0001586", "id": "MONDO:0001586", "label": "mucopolysaccharidosis type 1", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1831", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/ei/1/1832", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "At least 1 patient with this variant had documented IDUA deficiency within the affected range in leukocytes, a significant reduction in urine GAGs upon treatment with enzyme replacement therapy, and clinical features specific to MPS I including arthropathy, corneal involvement, and valvular thickening. (PP4_Moderate).\n", "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1831", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1636", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/ei/1/1637", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4.1.0 is 0.00004241 (50/1178952 alleles) in the European (non-Finnish) population, which is lower than the ClinGen Lysosomal Diseases VCEP’s threshold for PM2_Supporting (<0.00025), meeting this criterion (PM2_Supporting).", "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1636", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1651", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/ei/1/1652", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "This variant has been detected in at least 10 individuals with MPS I, all compound heterozygous for the variant and another variant in IDUA that has been classified as pathogenic for MPS I by the ClinGen LD VCEP, all phase unconfirmed, including c.208C>T (p.Gln70Ter) (PMID: 28752568, ClinVar Variation ID: 11909, 0.5 points), c.1205G>A (p.Trp402Ter) (PMID: 28752568, CinVar Variation ID: 11908, 7 patients, max 2 x 0.5 points), and (c.1029C>G (p.Tyr343Ter) (C;inVar Variation ID: 550474, clinical lab, 0.5 points) (PM3_Strong). Total 2 points (PM3_Strong).", "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1651", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1762", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/ei/1/1763", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA356990/MONDO:0001586/091/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "The NM_000203.5: c.590-7G>A variant in IDUA occurs within the splice acceptor site motif of intron 5. RT-PCR analysis revealed skipping of biologically-relevant-exon 6/14, or, rarely,\nintron 5 inclusion, resulting mainly in splicing at nt -28 of intron 5, and also a very small amount of normal IDUA mRNA (PMID: 8213840; 9748610) (PVS1_Strong (RNA)).\n", "contributionDate": { "date": "2025/6/7", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA356990/MONDO:0001586/091/ci/CA356990/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091/0/1762", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA356990/MONDO:0001586/091", "metadata": { "created": "2025-06-07T19:45:14.051Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Sat, 07 Jun 2025 19:45:13 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "b97d1371-e9cc-45bc-9b2b-fb9084c93edc", "variant": { "@id": "https://reg.genome.network/allele/CA356990", "id": "CAR:CA356990", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000203.5(IDUA):c.590-7G>A" } ], "preferred": true }, { "alleleName": [ { "name": "NM_000203.5:c.590-7G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000203.5(IDUA):c.590-7G>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-05-31T18:56:33.321Z" } }, "status": { "code": 200, "name": "OK" } }