{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d20044ce-4787-4553-bd2d-0af11fd1ecb9/doc/sepio/version/1.2.0", "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/CA290956162/MONDO:0010119/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/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": "2022/12/7", "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/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA290956162/MONDO:0010119/011/ci/CA290956162/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": "The Leu86Pro variant has a REVEL score of 0.859 (threshold >0.7) meeting criteria for PP3.", "contributionDate": { "date": "2022/12/7", "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": "CA290956162/MONDO:0010119/011/ci/CA290956162/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/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": "2022/12/7", "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/CA290956162/MONDO:0010119/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA290956162/MONDO:0010119/011/ci/CA290956162/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": "The variant is absent from population databases, including gnomAD v2.1.1 and v3, meeting criteria for PM2.", "contributionDate": { "date": "2022/12/7", "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": "CA290956162/MONDO:0010119/011/ci/CA290956162/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/ei/1/1826", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2022/12/7", "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/0039", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0039", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA290956162/MONDO:0010119/011/ci/EV000001226", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "cDNA constructs bearing the wild‐type αIIb containing Leu86 or mutants, Pro86, Gln86 and Arg86 were generated to transfect COS7 cells along with wild-type β3 constructs. Surface expression of αIIbβ3, measured by flow cytometry, was remarkably reduced in cell transfected with Pro86 (mean relative values: 12·7% & 14·7%; Figure 2) compared to wild-type αIIb. In contrast, the Gln86 and Arg86 mutants showed expression levels similar to wild type.", "contributionDate": { "date": "2022/12/7", "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": "CA290956162/MONDO:0010119/011/ci/EV000001226", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12181054", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/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": "2022/12/7", "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/CA290956162/MONDO:0010119/011/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA290956162/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": "GT64 is a 26yo female of French ancestry, with epistaxis, mouth and tonsil bleeding, easy bruising, menorrhagia, and a bleeding score of 3. She had gingivorrhagia and ecchymoses as an adult and has received RBC and platelet transfusion. Platelet aggregation was absent with 3 agonists, but normal with ristocetin. αIIbβ3 expression assessed by flow cytometry was <5%. She is compound heterozygous for Leu86Pro and c.1440-13_1440-1del. Phase was not confirmed.", "contributionDate": { "date": "2022/12/7", "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": "CA290956162/MONDO:0010119/011/ci/EV000001237", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25728920", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA290956162/MONDO:0010119/011/ci/EV000001226", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "21y/F with history of purpura and epistaxis. The authors note that flow cytometry and western blotting revealed markedly reduced expression of integring αIIbβ3, but data is not shown. The patient was compound heterozygous for Leu86Pro (inherited from father) and Gln778Pro (inherited from monther), confirmed in trans. No information on CBC, platelet morphology, LTA analysis.", "contributionDate": { "date": "2022/12/7", "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": "CA290956162/MONDO:0010119/011/ci/EV000001226", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12181054", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/MONDO:0010119/011/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA290956162/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": "2022/12/7", "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/CA290956162/MONDO:0010119/011/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA290956162/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": "Proband GT64 is compound heterozygous for this variant and the c.1440-13_1440-1del variant, which is classified as pathogenic by the Platelet Disorders VCEP. Since phase is not confirmed in this proband, 0.5 pts is applied towards PM3 scoring.", "contributionDate": { "date": "2022/12/7", "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": "CA290956162/MONDO:0010119/011/ci/EV000001237", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25728920", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA290956162/MONDO:0010119/011", "metadata": { "created": "2024-09-28T00:56:24.996Z", "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 00:56:24 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "d20044ce-4787-4553-bd2d-0af11fd1ecb9", "variant": { "@id": "https://reg.genome.network/allele/CA290956162", "id": "CAR:CA290956162", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000419.4:c.257T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000419.4:c.257T>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-31T10:54:52.450Z" } }, "status": { "code": 200, "name": "OK" } }