{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/affdd230-5d28-41fd-b2b3-098410612dc1/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/CA638504295/MONDO:0009276/082/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/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": "2025/2/17", "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/CA638504295/MONDO:0009276/082/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA638504295/MONDO:0009276/082/ci/CA638504295/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.448del (p.Ala150ArgfsTer?) variant in GP1BB is a frameshift variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove <10%, affecting the critical transmembrane domain (PVS1_Strong).", "contributionDate": { "date": "2025/2/17", "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": "CA638504295/MONDO:0009276/082/ci/CA638504295/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/MONDO:0009276/082/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/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": "2025/2/17", "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/CA638504295/MONDO:0009276/082/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA638504295/MONDO:0009276/082/ci/CA638504295/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": "2025/2/17", "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": "CA638504295/MONDO:0009276/082/ci/CA638504295/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/MONDO:0009276/082/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/MONDO:0009276/082/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": "2025/2/17", "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/CA638504295/MONDO:0009276/082/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA638504295/MONDO:0009276/082/ci/CA638504295/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": "Surface expression of GP1a and GP1b and GP9 measured by flow cytometry in 293T cells transiently co-transfected with the GP1b c.448del variant and wild type GP1a and GP9 showed decreased expression at 0% (<25%) WT levels, indicating that this variant impacts protein function (PMID:16978236)(PS3_supporting).", "contributionDate": { "date": "2025/2/17", "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": "CA638504295/MONDO:0009276/082/ci/CA638504295/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/MONDO:0009276/082/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/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": "2025/2/17", "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/CA638504295/MONDO:0009276/082/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA638504295/MONDO:0009276/082/ci/CA638504295/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.448del variant has been found in at least one individual with BSS, compound heterozygous for this variant and the Likely Pathogenic p.Cys147Ser, not considered here to avoid circularity.", "contributionDate": { "date": "2025/2/17", "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": "CA638504295/MONDO:0009276/082/ci/CA638504295/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/MONDO:0009276/082/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/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": "2025/2/17", "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/CA638504295/MONDO:0009276/082/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA638504295/MONDO:0009276/082/ci/CA638504295/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": "Heterozygous L-5 is reported with macrothrombocytopenia (47x10^9 platelets/l; MPV not provided) 0pt; H-7 macrothrombocytopenia (120x10^9 platelets/l; MPV not provided) 0pt\n\nPS4_NotMet due to missing MPV information", "contributionDate": { "date": "2025/2/17", "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": "CA638504295/MONDO:0009276/082/ci/CA638504295/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/MONDO:0009276/082/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA638504295/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": "2025/2/17", "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/CA638504295/MONDO:0009276/082/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA638504295/MONDO:0009276/082/ci/CA638504295/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 0.00001079 (based on 2/30690 alleles) in the East Asian population, which is below the <0.0000651678 threshold for PM2_supporting.\n", "contributionDate": { "date": "2025/2/17", "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": "CA638504295/MONDO:0009276/082/ci/CA638504295/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA638504295/MONDO:0009276/082", "metadata": { "created": "2025-02-17T15:35:28.203Z", "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": "Mon, 17 Feb 2025 15:35:28 -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": "affdd230-5d28-41fd-b2b3-098410612dc1", "variant": { "@id": "https://reg.genome.network/allele/CA638504295", "id": "CAR:CA638504295", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000407.5:c.448del" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000407.5(GP1BB):c.448del (p.Ala150fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T02:33:48.615Z" } }, "status": { "code": 200, "name": "OK" } }