{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d91ee10f-1f19-432f-a68e-c32a9dff069f/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:0015630", "id": "MONDO:0015630", "label": "von Willebrand disease type 2M", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/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": "2025/10/10", "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/CA228715/MONDO:0015630/081/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "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 0.687, which is above the ClinGen VWD VCEP threshold of >0.644 and predicts a damaging effect on VWF function (PP3).\n", "contributionDate": { "date": "2025/10/10", "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": "CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/10/10", "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/CA228715/MONDO:0015630/081/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "A hydrodynamic mouse model expressing the p.Ser1783Ala variant showed severely reduced type I and type III collagen binding, indicating that this variant has a damaging effect on protein function (PMID: 25051961)(PS3).\n\nCollagen binding assay performed with the c.5347T>G (p.Ser1783Ala) recombinant mutant and wt vWF expressed in HEK293 cells showed decreased binding indicating that this variant has a damaging effect on protein function (PMID: 19687512)(PS3_supporting).\n\n", "contributionDate": { "date": "2025/10/10", "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": "CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/10/10", "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/CA228715/MONDO:0015630/081/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "Although an additional VWD patient asserted was found who carried this variant, the patient had a VWF:RCo/VWF:Ag ratio greater than 0.7 as well as normal collagen binding. ", "contributionDate": { "date": "2025/10/10", "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": "CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2025/10/10", "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/CA228715/MONDO:0015630/081/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "The Grpmax filtering allele frequency in gnomAD v4.1 is 0.0005233 (based on 63/91072 alleles in the South Asian population). This intermediate allele frequency is lower than the ClinGen VWD VCEP threshold (>0.01) for BS1 but higher than the threshold of <0.0001 for type 2M for PM2_Supporting. \n\n\t", "contributionDate": { "date": "2025/10/10", "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": "CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA228715/MONDO:0015630/081/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": "2025/10/10", "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/CA228715/MONDO:0015630/081/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "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 1 patient with this variant displayed excessive mucocutaneous bleeding as well as laboratory phenotypes of a normal multimer pattern, low VWF:RCo/VWF:Ag ratio and abnormal collagen binding assay, which together are highly specific for VWD type 2M. (PP4_moderate, PMID: 19687512). \n\n", "contributionDate": { "date": "2025/10/10", "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": "CA228715/MONDO:0015630/081/ci/CA228715/MONDO:0015630/081.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA228715/MONDO:0015630/081", "metadata": { "created": "2025-10-10T19:50:37.706Z", "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, 10 Oct 2025 19:50:37 -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": "d91ee10f-1f19-432f-a68e-c32a9dff069f", "variant": { "@id": "https://reg.genome.network/allele/CA228715", "id": "CAR:CA228715", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000552.5:c.5347T>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000552.5(VWF):c.5347T>G (p.Ser1783Ala)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T17:04:45.473Z" } }, "status": { "code": 200, "name": "OK" } }