{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/25b5ead3-1e18-41ec-96a3-f00739412896/doc/sepio/version/1.2.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528071527", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP1BB 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/CA410676959/MONDO:0009276/082/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/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": "2025/2/18", "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/CA410676959/MONDO:0009276/082/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "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 (PM2_Supporting).", "contributionDate": { "date": "2025/2/18", "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": "CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/18", "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/CA410676959/MONDO:0009276/082/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Another missense variant in the same codon has been reported in a patient with Bernard-Soulier syndrome c.268C>T (p.Pro90Ser) (PMID:25539746; classified Likely Pathogenic by the PD VCEP). However, this variant is not considered here to avoid circularity.", "contributionDate": { "date": "2025/2/18", "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": "CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/18", "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/CA410676959/MONDO:0009276/082/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "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 0.853, which is above the ClinGen PD VCEP threshold of >0.773 and predicts a damaging effect on function (PP3_Moderate).", "contributionDate": { "date": "2025/2/18", "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": "CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/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": "2025/2/18", "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/CA410676959/MONDO:0009276/082/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "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 probands with Bernard-Soulier syndrome. One proband was homozygous for the variant (PMID: 21699652). Total points: .5 (PM3_supporting).", "contributionDate": { "date": "2025/2/18", "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": "CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1609", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410676959/MONDO:0009276/082/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": "2025/2/18", "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/CA410676959/MONDO:0009276/082/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "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 BS-15 in PMID:21699652) with this variant had aggregation absent for ristocetin and present for all other agonists and 10% expression of GP1bb measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome and with full gene sequencing and del/dup analysis of all BSS genes is specific to GPIba, GP1bb, and GP9 (PP4_moderate). Additionally, the patient had excessive mucocutaneous bleeding which is consistent with Bernard-Soulier syndrome.", "contributionDate": { "date": "2025/2/18", "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": "CA410676959/MONDO:0009276/082/ci/CA410676959/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410676959/MONDO:0009276/082", "metadata": { "created": "2025-02-18T15:42:17.508Z", "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, 18 Feb 2025 15:42:17 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "25b5ead3-1e18-41ec-96a3-f00739412896", "variant": { "@id": "https://reg.genome.network/allele/CA410676959", "id": "CAR:CA410676959", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000407.5:c.269C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000407.5:c.269C>G" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-26T06:34:26.765Z" } }, "status": { "code": 200, "name": "OK" } }