{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/982aceca-eaa9-4feb-a56c-15396353f2a2/doc/sepio/version/3.0.0", "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/CA400025722/MONDO:0100326/011/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/MONDO:0100326/011/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/27", "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/CA400025722/MONDO:0100326/011/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400025722/MONDO:0100326/011/ci/EV000001456", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Mutant β3 cDNA possessing A at position 1009 that leads to Asn304, was constructed using a site-directed mutagenesis kit, and cloned into expression vector pSG5. WT β3/pSG5 or the mutant β3 cDNA/pSG5 were cotransfected into COS7 cells with WT αIIb/pSG5. Forty-eight hours after transfection, harvested COS7 cells were incubated with PE-CD41a, which recognizes the αIIbβ3 complex, and the percentage of positive transfected cells was determined by flow cytometry. The mean values of 27% of COS7 cells transfected with WT αIIb/pSG5 and WT β3/pSG5 were positive for the PE-conjugated monoclonal antibody against αIIbβ3. On the other hand, only 4% of COS7 cells transfected with WT αIIb/pSG5 and Ile304Asn β3/pSG5 possessing A at position 1009 were positive (15% of the WT level). In addition, immunoprecipitation analysis indicated the absence of αIIbβ3 inside COS7 cells transfected with mutant β3 cDNA. \n\nThis evidence was downgraded to PS3_Supporting because the level of αIIb, β3, and αIIbβ3 cell surface expression was not reported, only whether cells were positive or negative for surface αIIb, β3, and αIIbβ3.", "contributionDate": { "date": "2025/2/27", "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": "CA400025722/MONDO:0100326/011/ci/EV000001456", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/15634267", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/MONDO:0100326/011/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/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": "2025/2/27", "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/CA400025722/MONDO:0100326/011/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400025722/MONDO:0100326/011/ci/CA400025722/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 (in PMID: 15634267) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was remarkably reduced, as measured by flow cytometry. However, ITGA2B and ITGB3 were not reported to be sequenced across all exons and intron/exon boundaries.", "contributionDate": { "date": "2025/2/27", "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": "CA400025722/MONDO:0100326/011/ci/CA400025722/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/MONDO:0100326/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/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": "2025/2/27", "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/CA400025722/MONDO:0100326/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400025722/MONDO:0100326/011/ci/CA400025722/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": "2025/2/27", "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": "CA400025722/MONDO:0100326/011/ci/CA400025722/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/MONDO:0100326/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/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": "2025/2/27", "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/CA400025722/MONDO:0100326/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400025722/MONDO:0100326/011/ci/CA400025722/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 0.97, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on function (PP3).", "contributionDate": { "date": "2025/2/27", "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": "CA400025722/MONDO:0100326/011/ci/CA400025722/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/MONDO:0100326/011/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400025722/MONDO:0100326/011/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": "2025/2/27", "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/CA400025722/MONDO:0100326/011/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400025722/MONDO:0100326/011/ci/CA400025722/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 patient in PMID: 15634267 is compound heterozygous for the maternal Ile330Asn and paternal His306Pro (classified Likely Pathogenic by the PD-VCEP) variants. ", "contributionDate": { "date": "2025/2/27", "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": "CA400025722/MONDO:0100326/011/ci/CA400025722/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400025722/MONDO:0100326/011", "metadata": { "created": "2025-02-27T13:31:32.171Z", "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, 27 Feb 2025 13:31:32 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "3.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "982aceca-eaa9-4feb-a56c-15396353f2a2", "variant": { "@id": "https://reg.genome.network/allele/CA400025722", "id": "CAR:CA400025722", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000212.3:c.989T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000212.3:c.989T>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T04:20:29.372Z" } }, "status": { "code": 200, "name": "OK" } }