{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/3cba4d4c-64ad-4e93-a2f6-e178841f7086/doc/sepio/version/1.1.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637583", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1", "type": "VariantPathogenicityInterpretationGuideline", "url": "https://clinicalgenome.org/docs/clingen-platelet-disorders-expert-panel-specifications-to-the-acmg-amp-variant-interpretation-guidelines-version-2.1/", "version": "2.1.0" }, "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/CA399805900/MONDO:0100326/011/el/0/1774", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/ei/1/1775", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/5/2", "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/CA399805900/MONDO:0100326/011/el/0/1774/1776", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805900/MONDO:0100326/011/ci/CA399805900/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": "Another missense variant c.475G>A (p.Gly159Ser) [PMID: 16359515] in the same codon has been classified Likely Pathogenic for Glanzmann thrombasthenia by the ClinGen PD VCEP.", "contributionDate": { "date": "2025/5/2", "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": "CA399805900/MONDO:0100326/011/ci/CA399805900/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1774/1776", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/1/1775", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1774", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/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": "2025/5/2", "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/CA399805900/MONDO:0100326/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805900/MONDO:0100326/011/ci/CA399805900/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 computational predictor REVEL gives a score of 0.751, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on ITGB3 function (PP3).", "contributionDate": { "date": "2025/5/2", "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": "CA399805900/MONDO:0100326/011/ci/CA399805900/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/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": "2025/5/2", "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/CA399805900/MONDO:0100326/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805900/MONDO:0100326/011/ci/CA399805900/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": "This variant is absent from gnomAD v4.1 (PM2_Supporting).", "contributionDate": { "date": "2025/5/2", "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": "CA399805900/MONDO:0100326/011/ci/CA399805900/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/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": "2025/5/2", "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/CA399805900/MONDO:0100326/011/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805900/MONDO:0100326/011/ci/CA399805900/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": "P2 (PMID: 34275420) is homozygous for this variant (PM3_supporting).", "contributionDate": { "date": "2025/5/2", "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": "CA399805900/MONDO:0100326/011/ci/CA399805900/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1609", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/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": "2025/5/2", "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/CA399805900/MONDO:0100326/011/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805900/MONDO:0100326/011/ci/EV000001480", "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 COS-7 cells transiently co-transfected with Gly159Val variant αIIb and wild type β3 showed normal expression levels (PS3_NotMet).\n\nTesting of fibrinogen binding function of the expressed protein was not reported.\n\nThe authors suggest that the c.476G>T variant may instead affect splicing; and report that the Human Splice Finder tool predicted that the αIIb:c.476 G > T SNV might create a cryptic donor splicing site in exon 4 leading to a frame shift (αIIb:p.Gly159Alafs). This splice impact is not predicted by SpliceAI and was not confirmed in patient cDNA or mini-gene assay.", "contributionDate": { "date": "2025/5/2", "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": "CA399805900/MONDO:0100326/011/ci/EV000001480", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/34275420", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805900/MONDO:0100326/011/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": "2025/5/2", "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/CA399805900/MONDO:0100326/011/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805900/MONDO:0100326/011/ci/CA399805900/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 1 in PMID: 34275420) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Platelet surface expression of the αIIbβ3 complex was not tested by these authors though the patient was reported as type I GT from local lab in Turkey by flow cytometry analysis.", "contributionDate": { "date": "2025/5/2", "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": "CA399805900/MONDO:0100326/011/ci/CA399805900/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805900/MONDO:0100326/011", "metadata": { "created": "2025-05-15T16:08:27.816Z", "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, 15 May 2025 16:08:27 -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": "3cba4d4c-64ad-4e93-a2f6-e178841f7086", "variant": { "@id": "https://reg.genome.network/allele/CA399805900", "id": "CAR:CA399805900", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000419.5:c.476G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000419.5(ITGA2B):c.476G>T (p.Gly159Val)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T08:09:18.234Z" } }, "status": { "code": 200, "name": "OK" } }