{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/dbb0136b-f516-4fb1-9771-b243432556e2/doc/sepio/version/1.1.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100326", "id": "MONDO:0100326", "label": "Glanzmann thrombasthenia", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/3/6", "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/CA400029054/MONDO:0100326/011/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029054/MONDO:0100326/011/ci/CA400029054/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The variant has been reported to segregate with Glanzmann thrombasthenia in the proband plus one affected family member, both with the homozygous Cys463Ser genotype. 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PM2_Supporting).", "contributionDate": { "date": "2025/3/6", "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": "CA400029054/MONDO:0100326/011/ci/CA400029054/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/ei/1/1739", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/3/6", "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/CA400029054/MONDO:0100326/011/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029054/MONDO:0100326/011/ci/CA400029054/MONDO:0100326/011.002", "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 7 in PMID34267460) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to 0.5-1.7%, as measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries. (PP4_strong)", "contributionDate": { "date": "2025/3/6", "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": "CA400029054/MONDO:0100326/011/ci/CA400029054/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/3/6", "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/CA400029054/MONDO:0100326/011/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029054/MONDO:0100326/011/ci/EV000001454", "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 αIIbβ3 measured by flow cytometry in BHK cells transiently co-transfected with Cys463Ser (here referred to as Cys437Ser) variant β3 and wild type αIIb showed decreased expression at 40% WT levels of positive cells. This modest reduction is insufficient to apply PS3.", "contributionDate": { "date": "2025/3/6", "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": "CA400029054/MONDO:0100326/011/ci/EV000001454", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/22308022", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029054/MONDO:0100326/011/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": "2025/3/6", "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/CA400029054/MONDO:0100326/011/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029054/MONDO:0100326/011/ci/CA400029054/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Patient 7 of PMID: 34267460 is homozygous for this variant (0.5pt; PM3_supporting).\t", "contributionDate": { "date": "2025/3/6", "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": "CA400029054/MONDO:0100326/011/ci/CA400029054/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029054/MONDO:0100326/011", "metadata": { "created": "2025-03-06T22:02:00.756Z", "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, 06 Mar 2025 22:02:00 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "dbb0136b-f516-4fb1-9771-b243432556e2", "variant": { "@id": "https://reg.genome.network/allele/CA400029054", "id": "CAR:CA400029054", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000212.3:c.1388G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000212.3:c.1388G>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T12:15:15.850Z" } }, "status": { "code": 200, "name": "OK" } }