{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/4d0d306d-ad40-4e0f-8278-e402d15ad508/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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4.1.0. is 8.522e-7 (1/1173452 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": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1672", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1673", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1672/1674", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": 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"EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1789", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1790", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1789/1791", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { 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", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1663", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1664", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "This variant has not been reported as a de novo change.", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1663/1665", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1664", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1663", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1768", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1769", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1768/1770", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Lack of familial segregation has not been reported for this variant. ", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1768/1770", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1769", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1768", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1579", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1580", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1579/1581", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "There is no known alternate molecular basis for deficiency of alpha-L-iduronidase activity, other than variants in IDUA.", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1579", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "This is a missense variant: this criterion does not apply. ", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/EV000001832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Prommajan et al. (2011) transiently transfected the c.826G>A variant into COS-7 cells. The experiment was performed twice in triplicate, included a positive and negative control and accounted for the background IDUA activity in COS-7 cells, though there was no evidence that sequencing was used to confirm that the engineered mutation was present in the COS-7 cells after site-directed mutagenesis. Once the background enzyme activity is subtracted out, the residual enzyme activity is around 1%. Overall this appears to meet criteria in itself to apply PS3_Supporting. ", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/EV000001832", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/21364962", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.833 which is above the threshold of 0.773, evidence that correlates with impact to IDUA function at the moderate level based on the specifications of the ClinGen Lysosomal Diseases VCEP (PMID: 36413997) (PP3_Moderate).", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "This variant does not involve one of the specific residues known to be crucial to the function of IDUA.", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Co-segregation in multiple affected family members has not been reported for this variant. ", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Patient 2 from PMID 21364962 has two (claw hand deformity i.e. arthropathy and corneal opacity) specific clinical features of MPS (one criterion met). They also have alpha-L-iduronidase enzyme activity that is well outside the normal range (0.61 nmol/h/mg protein; mean and SD in controls of 23.10±8.80 nmol/h/mg protein)(second criterion met). Since two criteria are met, PP4 can be applied at its standard strength.", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "This variant has been detected in at least five probands with MPS I in the available literature. There is at least one homozygous patient of Thai ancestry (PMID 21364962), and three Turkish siblings (reported in PMID 23786846, but potentially the same proband as in PMID 21394825), scoring 1 point in total (max for homozygous individuals). Two individuals are compound heterozygous for the variant and another variant in IDUA that has been classified as pathogenic or likely pathogenic for MPS I including c.208C>T (p.Gln70Ter) (ClinVar Variation ID: 11909) (P by LD VCEP, phase unconfirmed, 0.5 points) (PMID: 35141277), and c.494-1G>A (ClinVar Variation ID: 557942) (LP by LD VCEP, phase unconfirmed, 0.25 points) (PMID: 21394825). Another individual is compound heterozygous for the variant and c.250G>C (p.Gly84Arg). The allelic data from the latter patient will be used in the classification of p.Gly84Arg and is not included here to avoid circular logic. Total 1.75 points (PM3)\n\n", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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://erepo.genome.network/evrepo/api/interpretation/CA355962355/MONDO:0001586/091/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "No pathogenic/likely pathogenic missense changes have been reported at this amino acid residue. There are two reports of the missense change c.828G>C causing p.(Glu276Asp), both of which have classified this variant as a variant of uncertain significance. ", "contributionDate": { "date": "2025/5/23", "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": "CA355962355/MONDO:0001586/091/ci/CA355962355/MONDO:0001586/091.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA355962355/MONDO:0001586/091", "metadata": { "created": "2025-05-30T23:24:29.775Z", "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": "Fri, 30 May 2025 23:24:29 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "4d0d306d-ad40-4e0f-8278-e402d15ad508", "variant": { "@id": "https://reg.genome.network/allele/CA355962355", "id": "CAR:CA355962355", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001363576.1:c.430G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001363576.1:c.430G>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T02:16:35.801Z" } }, "status": { "code": 200, "name": "OK" } }