{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/231fb197-4be4-4ed0-b749-985409b65e2c/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/CA410677524/MONDO:0009276/082/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/MONDO:0009276/082/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": "2025/2/13", "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/CA410677524/MONDO:0009276/082/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677524/MONDO:0009276/082/ci/CA410677524/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 1 in PMID: 23566026) with this variant had less than 10% expression of GPIba and GP9 compared to controls. The patient also had excessive mucocutaneous bleeding and macrothrombocytopenia which are consistent with Bernard-Soulier syndrome. Full gene sequencing of GP1BA, GP1BB, and GP9 were performed as well as del/dup analysis (PP4_Moderate). \n\n", "contributionDate": { "date": "2025/2/13", "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": "CA410677524/MONDO:0009276/082/ci/CA410677524/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/MONDO:0009276/082/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/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": "2025/2/13", "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/CA410677524/MONDO:0009276/082/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677524/MONDO:0009276/082/ci/CA410677524/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 7.700e-7 (based on 3/1034782 alleles) in the European (non-Finnish) population, which is below the <0.0000651678 threshold for PM2_supporting.\n\n", "contributionDate": { "date": "2025/2/13", "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": "CA410677524/MONDO:0009276/082/ci/CA410677524/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/MONDO:0009276/082/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/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": "2025/2/13", "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/CA410677524/MONDO:0009276/082/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677524/MONDO:0009276/082/ci/CA410677524/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 2 unrelated probands with Bernard-Soulier syndrome. \nOne proband was homozygous for the variant (0.5 points, PMID: 12447957). The second proband was compound heterozygous for this variant and a pathogenic or likely pathogenic variant that was confirmed in trans by parental testing (22q11.2 deletion of GP1BB, 1 point, PMID: 23566026). PM3_Moderate. NM_000407.5(GP1BB):c.443G>A (p.Trp148Ter) was found on maternal allele, 22q11.2 deletion found on paternal allele. \n\n\n", "contributionDate": { "date": "2025/2/13", "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": "CA410677524/MONDO:0009276/082/ci/CA410677524/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/MONDO:0009276/082/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/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": "2025/2/13", "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/CA410677524/MONDO:0009276/082/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677524/MONDO:0009276/082/ci/CA410677524/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.443G>A (p.Trp148Ter) 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 > 10% (28%) of the protein (PVS1_Strong). \n", "contributionDate": { "date": "2025/2/13", "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": "CA410677524/MONDO:0009276/082/ci/CA410677524/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/MONDO:0009276/082/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA410677524/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": "2025/2/13", "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/CA410677524/MONDO:0009276/082/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA410677524/MONDO:0009276/082/ci/CA410677524/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 GP1b and GP9 measured by flow cytometry and Western blot in HEK293T cells transiently co-transfected with the NM_000407.5:c.443G>A variant GP1b and wild type GP1b showed decreased expression at 0% WT levels, indicating that this variant impacts protein function (PMID: 12447957)(PS3_supporting).\n\n", "contributionDate": { "date": "2025/2/13", "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": "CA410677524/MONDO:0009276/082/ci/CA410677524/MONDO:0009276/082.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082/0/1696", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA410677524/MONDO:0009276/082", "metadata": { "created": "2025-02-14T21:36:55.314Z", "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 21:36:55 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "231fb197-4be4-4ed0-b749-985409b65e2c", "variant": { "@id": "https://reg.genome.network/allele/CA410677524", "id": "CAR:CA410677524", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000407.5:c.443G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000407.5(GP1BB):c.443G>A (p.Trp148Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-21T15:11:26.550Z" } }, "status": { "code": 200, "name": "OK" } }