{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/2a3e00c1-568c-483f-b048-6a9f3000f56a/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1529372862", "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:0015631", "id": "MONDO:0015631", "label": "von Willebrand disease type 2N", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/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": "2024/11/6", "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/CA383520062/MONDO:0015631/090/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "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 low FVIII activity and decreased VWF:FVIII binding, which is highly specific for VWD type 2N. (PP4_moderate, PMID 26988807). Additional consistent phenotypes were also reported in the patient including normal VWF:Ag, and normal HMW multimers.\n", "contributionDate": { "date": "2024/11/6", "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": "CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2024/11/6", "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/CA383520062/MONDO:0015631/090/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "Segretation is asserted but affected status of other family members is not confirmed.", "contributionDate": { "date": "2024/11/6", "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": "CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/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": "2024/11/6", "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/CA383520062/MONDO:0015631/090/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "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 0.626, which is below the ClinGen VWD VCEP PP3 threshold of >0.644 and does not predict a damaging effect on VWF function. Additionally, the computational splicing predictor SpliceAI indicated that the variant has no impact on splicing.", "contributionDate": { "date": "2024/11/6", "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": "CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/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": "2024/11/6", "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/CA383520062/MONDO:0015631/090/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "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": "2024/11/6", "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": "CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "contributionDate": { "date": "2024/11/6", "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/CA383520062/MONDO:0015631/090/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "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 has been detected in 1 individual with von Willebrand Disease type 2N. The individual is compound heterozygous for the variant and a type 2N pathogenic variant as determined by the ClinGen VWD VCEP, confirmed in trans by the authors (p.Arg854Gln) (PM3, PMID 26988807).\n", "contributionDate": { "date": "2024/11/6", "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": "CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA383520062/MONDO:0015631/090/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": "2024/11/6", "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/CA383520062/MONDO:0015631/090/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50051_EP172323000528245", "id": "CG-PCER-AGENT:CG_50051_EP172323000528245", "type": "Agent" }, "comments": "Another missense variant c.2635G>A, p.Asp879Asn (PMIDs 9845532, 34298581) in the same codon has been classified as pathogenic for VWD type 2N by the ClinGen VWD VCEP (PM5). Splicing prediction using SpliceAI revealed no expected effects on splicing due to any of these variants.", "contributionDate": { "date": "2024/11/6", "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": "CA383520062/MONDO:0015631/090/ci/CA383520062/MONDO:0015631/090.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA383520062/MONDO:0015631/090", "metadata": { "created": "2024-11-06T17:58:57.202Z", "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": "Wed, 06 Nov 2024 17:58:57 -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": "2a3e00c1-568c-483f-b048-6a9f3000f56a", "variant": { "@id": "https://reg.genome.network/allele/CA383520062", "id": "CAR:CA383520062", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000552.5:c.2637C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000552.5:c.2637C>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-26T23:45:38.917Z" } }, "status": { "code": 200, "name": "OK" } }