{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/42cd378a-1c69-4e17-921c-a6d05ff77a09/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1527857178", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP1BA Version 1.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.1.0" }, "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/CA397318014/MONDO:0009276/079/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/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": "2026/2/5", "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/CA397318014/MONDO:0009276/079/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The largest population MAF allele frequency in gnomAD v4.1.0 is 0.000001695 (based on 2/1179886 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001114; PM2_Supporting).\n", "contributionDate": { "date": "2026/2/5", "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": "CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/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": "2026/2/5", "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/CA397318014/MONDO:0009276/079/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "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 0.653, which is above the ClinGen PD VCEP threshold of >0.644 and predicts a damaging effect on function (PP3).", "contributionDate": { "date": "2026/2/5", "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": "CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/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": "2026/2/5", "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/CA397318014/MONDO:0009276/079/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "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 (internal case from Versiti) with this variant had less than 10% expression of GPIba measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome Additionally, the patient had excessive mucocutaneous bleeding which are consistent with Bernard-Soulier syndrome (PP4). \n\n", "contributionDate": { "date": "2026/2/5", "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": "CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/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": "2026/2/5", "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/CA397318014/MONDO:0009276/079/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "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, Cys225 GP1BA that is defined as a critical functional domain by the ClinGen PD VCEP (PM1). ", "contributionDate": { "date": "2026/2/5", "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": "CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2026/2/5", "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/CA397318014/MONDO:0009276/079/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Another missense variant (c.673T>A, p.Cys225Ser) in the same codon has been classified as Pathogenic for Bernard-Soulier syndrome by the ClinGen PD VCEP (PM5). \n", "contributionDate": { "date": "2026/2/5", "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": "CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397318014/MONDO:0009276/079/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": "2026/2/5", "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/CA397318014/MONDO:0009276/079/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "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 (internal case from Versiti). This individual was compound heterozygous for this variant and the NM_000173.7(GP1BA):c.1601_1602del (p.Tyr534CysfsTer?) variant which was classified as Pathogenic by the PD VCEP. These phase in this variants is unknown (0.5 points, PM3_Supporting). \n", "contributionDate": { "date": "2026/2/5", "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": "CA397318014/MONDO:0009276/079/ci/CA397318014/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397318014/MONDO:0009276/079", "metadata": { "created": "2026-02-05T22:14:11.402Z", "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": "Thu, 05 Feb 2026 22:14:11 -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": "42cd378a-1c69-4e17-921c-a6d05ff77a09", "variant": { "@id": "https://reg.genome.network/allele/CA397318014", "id": "CAR:CA397318014", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000173.7:c.673T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000173.7(GP1BA):c.673T>C (p.Cys225Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T01:10:28.251Z" } }, "status": { "code": 200, "name": "OK" } }