{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/41465704-1a3b-4e6f-a1c8-46e186157156/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/CA400029369/MONDO:0100326/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/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": "2023/11/3", "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/CA400029369/MONDO:0100326/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029369/MONDO:0100326/011/ci/CA400029369/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": "Absent from ExAC and gnomAD.", "contributionDate": { "date": "2023/11/3", "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": "CA400029369/MONDO:0100326/011/ci/CA400029369/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/MONDO:0100326/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/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": "2023/11/3", "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/CA400029369/MONDO:0100326/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029369/MONDO:0100326/011/ci/CA400029369/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": "SIFT (Damaging), Polyphen2-HDIV (probably Damaging), and Mutation Taster (disease causing) agree that this variant has a deleterious effect and the REVEL score is 0.909 (>0.7 threshold).", "contributionDate": { "date": "2023/11/3", "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": "CA400029369/MONDO:0100326/011/ci/CA400029369/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/MONDO:0100326/011/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/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": "2023/11/3", "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/CA400029369/MONDO:0100326/011/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029369/MONDO:0100326/011/ci/EV000001600", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The mutant β3 construct was transfected together with wild-type αIIb or wild-type αv into HEK293 cells, and the expression of αIIbβ3 and αvβ3 on the surface of stable transfected cells was analyzed by flow cytometry using mAbs that reacted against β3 (mAb AP3), αIIbβ3 (mAb Gi5), and αvβ3 (mAb 23C6) complex. Similar to wild-type, both mutant-transfected cells expressed a comparable amount of αIIbβ3 and αvβ3 heterodimers on the cell surface, confirming that Cys460Trp mutation did not significantly impair the surface expression of αIIbβ3 and αvβ3 integrin. Immunoblotting analysis showed that the mutant β3 migrated slightly slower in comparison with wild-type β3 isoform, indicating that the disruption of one disulfide bond due to Cys460Trp mutation alters the secondary structure of integrin αIIbβ3.\n\nFurther flow cytometry found the Cys460Trp mutation affects the binding of type II mAbs against HPA-1a(such as 26.4 and B2G1)", "contributionDate": { "date": "2023/11/3", "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": "CA400029369/MONDO:0100326/011/ci/EV000001600", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/32770549", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/MONDO:0100326/011/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/MONDO:0100326/011/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": "2023/11/3", "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/CA400029369/MONDO:0100326/011/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029369/MONDO:0100326/011/ci/EV000001240", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Patient GT2 heterozygous for Cys486Trp has severe bleeding symptoms and severely reduced platelet aggregation after stimulation with agonists such as collagen, adenosine diphosphate, arachidonic acid, adrenaline, and epinephrine. Ristocetin aggregation was almost normal. Decreased, <5% alphaIIb-beta3 expression was determined by flow cytometry. Platelet count and size were not mentioned.", "contributionDate": { "date": "2023/11/3", "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": "CA400029369/MONDO:0100326/011/ci/EV000001240", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25373348", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/MONDO:0100326/011/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400029369/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": "2023/11/3", "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/CA400029369/MONDO:0100326/011/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400029369/MONDO:0100326/011/ci/EV000001240", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Patient GT2 has the Trp11Arg variant (VUS) in trans with Cys486Trp. Phase is confirmed to be in trans.", "contributionDate": { "date": "2023/11/3", "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": "CA400029369/MONDO:0100326/011/ci/EV000001240", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25373348", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400029369/MONDO:0100326/011", "metadata": { "created": "2024-09-28T03:11:30.197Z", "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 03:11:29 -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": "41465704-1a3b-4e6f-a1c8-46e186157156", "variant": { "@id": "https://reg.genome.network/allele/CA400029369", "id": "CAR:CA400029369", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000212.2:c.1458C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000212.2:c.1458C>G" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T15:39:33.923Z" } }, "status": { "code": 200, "name": "OK" } }