{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/6d4e983d-0fd7-4362-b71c-a2e4fc24d230/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528072643", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP9 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009276", "id": "MONDO:0009276", "label": "Bernard-Soulier syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/12/10", "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/CA123183/MONDO:0009276/083/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "This variant has been detected in at least 1 proband with Bernard-Soulier syndrome (PMID: 12100158). This individual was homozygous for the variant (0.5 points, PM3_Supporting). \n", "contributionDate": { "date": "2025/12/10", "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": "CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1609", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/12/10", "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/CA123183/MONDO:0009276/083/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Surface expression of GP1a, GP1b, and GP9 measured by flow cytometry in CHO cells transiently co-transfected with c.20T>C (p.Leu7Pro) variant GP9 and wild type GP1a and GP1b showed absent expression, indicating that this variant impacts protein function (PMID: 12100158)(PS3_supporting).\n", "contributionDate": { "date": "2025/12/10", "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": "CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/12/10", "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/CA123183/MONDO:0009276/083/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "At least one patient (Patient 1 in PMID: 12100158) with this variant had aggregation absent for ristocetin and present for all other agonists and less than 10% expression of GPIba, GP1bb and GP9 measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome. Additionally, the patient had excessive mucocutaneous bleeding and macrothrombocytopenia which are consistent with Bernard-Soulier syndrome. Functional evidence meeting PS3_supporting is accepted in lieu of del/dup analysis, as it addresses concerns about misattribution of phenotypic effects to the variant due to an undetected CNV(PP4_Moderate). \n\n", "contributionDate": { "date": "2025/12/10", "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": "CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/12/10", "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/CA123183/MONDO:0009276/083/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.731, which is above the ClinGen PD VCEP threshold of >0.644 and predicts a damaging effect on GP9 function (PP3).", "contributionDate": { "date": "2025/12/10", "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": "CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA123183/MONDO:0009276/083/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/12/10", "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/CA123183/MONDO:0009276/083/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).\n", "contributionDate": { "date": "2025/12/10", "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": "CA123183/MONDO:0009276/083/ci/CA123183/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA123183/MONDO:0009276/083", "metadata": { "created": "2025-12-10T18:35:51.486Z", "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, 10 Dec 2025 18:35:51 -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": "6d4e983d-0fd7-4362-b71c-a2e4fc24d230", "variant": { "@id": "https://reg.genome.network/allele/CA123183", "id": "CAR:CA123183", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000174.5:c.20T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000174.5(GP9):c.20T>C (p.Leu7Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T17:09:26.010Z" } }, "status": { "code": 200, "name": "OK" } }