{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/8ea2064e-3b97-47af-aef1-194ab06ebdf3/doc/sepio/version/1.0.0", "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/CA322080037/MONDO:0009276/082/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/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": "2025/2/14", "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/CA322080037/MONDO:0009276/082/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA322080037/MONDO:0009276/082/ci/CA322080037/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 (Patient 2 in PMID: 33217855) with this variant had impaired aggregation for ristocetin (aggregation in response to other agonists is not specifically mentioned). Additionally, this patient showed less than 10% expression of GPIba (0%) measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome. Full gene sequencing of all BSS genes was also performed for this patient by WES but analysis for structural variants was not performed. Additionally, the patient had excessive mucocutaneous bleeding and macrothrombocytopenia which are consistent with Bernard-Soulier syndrome (PP4). \n\n", "contributionDate": { "date": "2025/2/14", "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": "CA322080037/MONDO:0009276/082/ci/CA322080037/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/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": "2025/2/14", "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/CA322080037/MONDO:0009276/082/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA322080037/MONDO:0009276/082/ci/CA322080037/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 Grpmax filtering allele frequency in gnomaDv4.1 is 0.000002920 (based on 7/997364 alleles) in the European (non-Finnish) population, which is below the <0.0000651678 threshold for PM2_supporting.", "contributionDate": { "date": "2025/2/14", "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": "CA322080037/MONDO:0009276/082/ci/CA322080037/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA322080037/MONDO:0009276/082/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA322080037/MONDO:0009276/082/ci/CA322080037/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": "One patient heterozygous for Glu136Ter variant was reported (PMID: 36430862) with Thrombocytopenia (platelet count <150 × 109/L), platelet size = macro (MPV >12.8fl), 0.25pt", "contributionDate": { "date": "2025/2/14", "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": "CA322080037/MONDO:0009276/082/ci/CA322080037/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/ei/1/1763", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA322080037/MONDO:0009276/082/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA322080037/MONDO:0009276/082/ci/CA322080037/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 c.406G>T (p.Glu136Ter) variant in GP1BB is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove 34% (>10%) of the protein (PVS1_Strong). ", "contributionDate": { "date": "2025/2/14", "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": "CA322080037/MONDO:0009276/082/ci/CA322080037/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA322080037/MONDO:0009276/082/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA322080037/MONDO:0009276/082/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA322080037/MONDO:0009276/082/ci/CA322080037/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 detected in at least 1 proband with Bernard-Soulier syndrome (Patient 2 in PMID: 33217855) who was homozygous for the variant (0.5 PM3 points, PM3_Supporting). ", "contributionDate": { "date": "2025/2/14", "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": "CA322080037/MONDO:0009276/082/ci/CA322080037/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA322080037/MONDO:0009276/082", "metadata": { "created": "2025-02-14T21:37:15.590Z", "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": "Fri, 14 Feb 2025 21:37:15 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "8ea2064e-3b97-47af-aef1-194ab06ebdf3", "variant": { "@id": "https://reg.genome.network/allele/CA322080037", "id": "CAR:CA322080037", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000407.5:c.406G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000407.5(GP1BB):c.406G>T (p.Glu136Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-24T16:52:46.309Z" } }, "status": { "code": 200, "name": "OK" } }