{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b6180e8f-f45f-4279-8681-e3f31d75c9d0/doc/sepio/version/1.0.1", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010119", "id": "MONDO:0010119", "label": "Glanzmann's thrombasthenia", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0017", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000220", "id": "SEPIO:0000220", "label": "Pathogenic Very Strong" }, "id": "0017", "label": "PVS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA913203486/MONDO:0010119/011/ci/CA913203486/MONDO:0010119/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Ala31ProfsTer2 is a frameshift variant resulting from the 1-bp (G) deletion at nucleotide position 91, which causes premature termination at amino acid position 32 in exon 1 of 30. NMD is predicted.", "contributionDate": { "date": "2021/1/22", "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": "CA913203486/MONDO:0010119/011/ci/CA913203486/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/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": "2021/1/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/005", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "005", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA913203486/MONDO:0010119/011/ci/EV000001237", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "2 siblings, GT41a & GT41b, are compound heterozygous for this variant and Leu973AlafsTer63. GT41a is a 15yo female patient of Canadian and Chinese origins with frequent and severe epistaxis requiring hospital treatment (platelet and rFVIIa transfusion, nasal support, anti-fibrinolytic treatment) and easy bruising, with a WHO bleeding score of 4. Platelet aggregation was absent with 3 agonists, but normal with ristocetin. αIIbβ3 expression assessed by flow cytometry was <5%. She was compound heterozygous for Leu973Alafster63 & Ala31ProfsTer2, phase not confirmed. GT41b is a 13yo male patient of Canadian and Chinese origins with epistaxis, ecchymoses, easy bruising and a WHO bleeding score of 2. Treatment included administration of rFVIIa and anti-fibrinolytics. Platelet aggregation was absent with 3 agonists, but normal with ristocetin. αIIbβ3 expression assessed by flow cytometry was <5%. He was compound heterozygous for Leu973Alafster63 & Ala31ProfsTer2, phase not confirmed.", "contributionDate": { "date": "2021/1/22", "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": "CA913203486/MONDO:0010119/011/ci/EV000001237", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25728920", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA913203486/MONDO:0010119/011/ci/EV000001237", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/22", "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": "CA913203486/MONDO:0010119/011/ci/EV000001237", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25728920", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/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": "2021/1/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0060", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0060", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA913203486/MONDO:0010119/011/ci/EV000001237", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "GT41a and GT41b are siblings compound heterozygous for this variant and Leu973AlafsTer63. The variants have been confirmed to be in trans (Supp Fig 2) and therefore PP1 is applied.", "contributionDate": { "date": "2021/1/22", "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": "CA913203486/MONDO:0010119/011/ci/EV000001237", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25728920", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/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": "2021/1/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913203486/MONDO:0010119/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA913203486/MONDO:0010119/011/ci/CA913203486/MONDO:0010119/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Ala31ProfsTer2 is absent from population databases, including gnomAD, and meets criteria for PM2.", "contributionDate": { "date": "2021/1/22", "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": "CA913203486/MONDO:0010119/011/ci/CA913203486/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA913203486/MONDO:0010119/011", "metadata": { "created": "2024-09-28T05:58:47.390Z", "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": "Sat, 28 Sep 2024 05:58:47 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.1" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "b6180e8f-f45f-4279-8681-e3f31d75c9d0", "variant": { "@id": "https://reg.genome.network/allele/CA913203486", "id": "CAR:CA913203486", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000419.4:c.91del" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000419.4:c.91del" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T09:47:16.220Z" } }, "status": { "code": 200, "name": "OK" } }