{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/3f3d0c7b-a702-4ea7-a03a-15e8fc2e2fb8/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528062415", "label": "ClinGen von Willebrand Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for VWF Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015629", "id": "MONDO:0015629", "label": "von Willebrand disease type 2B", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/5/9", "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/CA383506185/MONDO:0015629/081/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "At least one patient with this variant displayed excessive mucocutaneous bleeding as well as a laboratory phenotypes of thrombocytopenia and an assay showing gain of function (flow cytometry showed markedly increased baseline activity), which together are highly specific for VWD type 2B. (PP4_moderate, SCV002515788.1). 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"evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/5/9", "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/CA383506185/MONDO:0015629/081/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.886, which is above the ClinGen VWD VCEP threshold of >0.644 and predicts a damaging effect on VWF function (PP3).", "contributionDate": { "date": "2025/5/9", "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": "CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/5/9", "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/CA383506185/MONDO:0015629/081/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1 (PM2_Supporting).", "contributionDate": { "date": "2025/5/9", "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": "CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383506185/MONDO:0015629/081/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/5/9", "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/CA383506185/MONDO:0015629/081/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "Another type 2B missense change (p.I1309V) has been reported at this amino acid residue and has been classified Pathogenic for type 2B VWD by the VWD VCEP.", "contributionDate": { "date": "2025/5/9", "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": "CA383506185/MONDO:0015629/081/ci/CA383506185/MONDO:0015629/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383506185/MONDO:0015629/081", "metadata": { "created": "2025-05-15T16:26:15.557Z", "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": "Thu, 15 May 2025 16:26:15 -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": "3f3d0c7b-a702-4ea7-a03a-15e8fc2e2fb8", "variant": { "@id": "https://reg.genome.network/allele/CA383506185", "id": "CAR:CA383506185", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000552.5:c.3926T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000552.5(VWF):c.3926T>A (p.Ile1309Asn)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-05T15:10:04.893Z" } }, "status": { "code": 200, "name": "OK" } }