{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fc507081-3d5a-4b36-8128-048f109aef1a/doc/sepio/version/1.2.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528071527", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP1BB Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009276", "id": "MONDO:0009276", "label": "Bernard-Soulier syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/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": "2025/2/18", "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/CA410677511/MONDO:0009276/082/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "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 0.687, which is above the ClinGen PD VCEP PP3 threshold of >0.644 and predicts a damaging effect on GP1BB function. And the computational splicing predictor SpliceAI indicated that the variant has no predicted impact on splicing.", "contributionDate": { "date": "2025/2/18", "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": "CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/18", "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/CA410677511/MONDO:0009276/082/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "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 (Proband in PMID:16978236) with this variant had aggregation absent for ristocetin and present for all other agonists, which is highly specific for Bernard-Soulier syndrome (PP4). Additionally, the patient had macrothrombocytopenia which is consistent with Bernard-Soulier syndrome.", "contributionDate": { "date": "2025/2/18", "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": "CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/18", "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/CA410677511/MONDO:0009276/082/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "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 resides at a disulfide bond residue, Cys147, of GP1BB that is defined as a critical functional domain by the ClinGen PD VCEP (PM1). ", "contributionDate": { "date": "2025/2/18", "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": "CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/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": "2025/2/18", "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/CA410677511/MONDO:0009276/082/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "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 has been found in at least one individual with BSS. This individual was compound heterozygous for this variant and the frameshift, c.448del, classified Likely Pathogenic. This variant was confirmed to be in trans via parental testing (1 point, PM3). ", "contributionDate": { "date": "2025/2/18", "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": "CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/el/0/1645", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/ei/1/1646", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/18", "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/CA410677511/MONDO:0009276/082/el/0/1645/1647", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677511/MONDO:0009276/082/ci/EV000001789", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The wild-type GPIba or mutant GPIbb cDNA construct\nwas transiently cotransfected with wild-type GPIba\nand GPIX cDNA constructs into 293T cells. The expression of GPIbb Ser1247 (referred to here as Ser122) polypeptide was similar to WT.\n\nNext, total expression of the recombinant GPIbb\nprotein and the formation of disulfide bonds\nbetween GPIba and GPIbb in the transfected cells\nwere investigated by immunoblot analysis. Only a small molecular weight band, corresponding to the individual GPIbb subunit, indicating there was not inter subunit disulfide bond.\n\nChinese hamster ovary cells stably expressing GPIba/Ibb Ser147/IX were surface labeled and immunoprecipitated, resulting in equal precipitation with WT and localized to the cell membrane similar to WT. It also had the ability to bind soluble vWF, measured by flow cytometry, and to aggregate in the presence of ristocetin. These results suggest that despite disruption of the disulfide linkage between GPIba and GPIbb, GPIb/IX is formed", "contributionDate": { "date": "2025/2/18", "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": "CA410677511/MONDO:0009276/082/ci/EV000001789", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16978236", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1645/1647", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/1/1646", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1645", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677511/MONDO:0009276/082/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": "2025/2/18", "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/CA410677511/MONDO:0009276/082/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Variant is absent from gnomADv4.1", "contributionDate": { "date": "2025/2/18", "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": "CA410677511/MONDO:0009276/082/ci/CA410677511/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677511/MONDO:0009276/082", "metadata": { "created": "2025-02-18T15:38:39.264Z", "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": "Tue, 18 Feb 2025 15:38:39 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "fc507081-3d5a-4b36-8128-048f109aef1a", "variant": { "@id": "https://reg.genome.network/allele/CA410677511", "id": "CAR:CA410677511", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000407.5:c.439T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000407.5:c.439T>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T16:24:25.823Z" } }, "status": { "code": 200, "name": "OK" } }