{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fb8a77c7-778b-45b9-b85e-90b1dc27f737/doc/sepio/version/2.0.0", "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/CA400030198/MONDO:0100326/011/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/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": "2024/3/8", "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/CA400030198/MONDO:0100326/011/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400030198/MONDO:0100326/011/ci/CA400030198/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": "Co-segregation of compound heterozygous genotype Cys549Ser and Gln254Lys with disease was observed in the proband and one affected sibling (PMID: 31088191).", "contributionDate": { "date": "2024/3/8", "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": "CA400030198/MONDO:0100326/011/ci/CA400030198/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/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": "2024/3/8", "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/CA400030198/MONDO:0100326/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400030198/MONDO:0100326/011/ci/CA400030198/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": "REVEL score of 0.885 is above the >.0.7 threshold in support of a deleterious effect.", "contributionDate": { "date": "2024/3/8", "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": "CA400030198/MONDO:0100326/011/ci/CA400030198/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/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": "2024/3/8", "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/CA400030198/MONDO:0100326/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400030198/MONDO:0100326/011/ci/CA400030198/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 at an extremely low frequency (below the <1/10,000 threshold) MAF of 0.00007557 (3/\t39696 alleles) in the gnomADv4.0 East Asian population.", "contributionDate": { "date": "2024/3/8", "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": "CA400030198/MONDO:0100326/011/ci/CA400030198/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/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": "2024/3/8", "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/CA400030198/MONDO:0100326/011/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400030198/MONDO:0100326/011/ci/CA400030198/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 2 compound heterozygous individuals have been reported with this variant in PMID: 31088191 confirmed in trans with c.2113del (Pathogenic, 1pt) and Gln254Lys (Likely Pathogenic; not included here to avoid circularity) respectively.", "contributionDate": { "date": "2024/3/8", "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": "CA400030198/MONDO:0100326/011/ci/CA400030198/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/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": "2024/3/8", "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/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400030198/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 Cys549Ser (here referred to as Cys523Ser) variant β3 and wild type αIIb showed decreased expression at 56% WT levels of positive cells. This modest reduction is insufficient to apply PS3 (PMID: 22308022).", "contributionDate": { "date": "2024/3/8", "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": "CA400030198/MONDO:0100326/011/ci/EV000001454", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/22308022", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/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": "2024/3/8", "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/0018", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0018", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400030198/MONDO:0100326/011/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400030198/MONDO:0100326/011/ci/CA400030198/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": "Both probands of PMID: 31088191 meet the criteria for PP4_Moderate; including mucocutaneous bleeding, and impaired aggregation with all agonists except ristocetin. Additionally, reduced surface expression of β3 was measured by flow cytometry at ~13% compared to normal.", "contributionDate": { "date": "2024/3/8", "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": "CA400030198/MONDO:0100326/011/ci/CA400030198/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400030198/MONDO:0100326/011", "metadata": { "created": "2024-09-28T04:09:33.487Z", "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 04:09:33 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "fb8a77c7-778b-45b9-b85e-90b1dc27f737", "variant": { "@id": "https://reg.genome.network/allele/CA400030198", "id": "CAR:CA400030198", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000212.3:c.1646G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000212.3:c.1646G>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T07:59:09.757Z" } }, "status": { "code": 200, "name": "OK" } }