{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/c4aa1004-6cff-4317-b302-93c0aeff6eea/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1576926543", "label": "ClinGen Hereditary Hemorrhagic Telangiectasia Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ENG Version 1.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0008535", "id": "MONDO:0008535", "label": "telangiectasia, hereditary hemorrhagic, type 1", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "contributionDate": { "date": "2025/3/25", "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/CA5252743/MONDO:0008535/136/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "comments": "Another missense variant, c.1517T>C, p.Leu506Pro (PMID: 24196379, 30073140; ClinVar Variation ID: 1774348), in the same codon has been classified as likely pathogenic for autosomal dominant Hereditary Hemorrhagic Telangiectasia by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel (PM5).", "contributionDate": { "date": "2025/3/25", "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": "CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "contributionDate": { "date": "2025/3/25", "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/CA5252743/MONDO:0008535/136/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "comments": "This variant has been reported in 2 probands with a phenotype consistent with HHT (PS4_Moderate; Internal lab contributors).", "contributionDate": { "date": "2025/3/25", "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": "CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "contributionDate": { "date": "2025/3/25", "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/CA5252743/MONDO:0008535/136/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.88, which is above the threshold of ≥0.644, evidence that correlates with impact to ENG function (PP3).", "contributionDate": { "date": "2025/3/25", "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": "CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA5252743/MONDO:0008535/136/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "contributionDate": { "date": "2025/3/25", "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/CA5252743/MONDO:0008535/136/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50037_EP171050563120248", "id": "CG-PCER-AGENT:CG_50037_EP171050563120248", "type": "Agent" }, "comments": "The overall minor allele frequency in gnomAD v2.1.1 is 0.000004 (1/250772 alleles), which is lower than the ClinGen Hereditary Hemorrhagic Telangiectasia VCEP threshold (<6 total alleles) for PM2_Supporting, meeting this criterion (PM2_Supporting). ", "contributionDate": { "date": "2025/3/25", "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": "CA5252743/MONDO:0008535/136/ci/CA5252743/MONDO:0008535/136.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA5252743/MONDO:0008535/136", "metadata": { "created": "2025-04-01T16:27:34.325Z", "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": "Tue, 01 Apr 2025 16:27:34 -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": "c4aa1004-6cff-4317-b302-93c0aeff6eea", "variant": { "@id": "https://reg.genome.network/allele/CA5252743", "id": "CAR:CA5252743", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001114753.3:c.1517T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001114753.3(ENG):c.1517T>A (p.Leu506His)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T13:13:49.599Z" } }, "status": { "code": 200, "name": "OK" } }