{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fc85773b-0c29-4638-9eb9-53a16007d383/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528072643", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP9 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/CA354447931/MONDO:0009276/083/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/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": "2026/1/20", "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/CA354447931/MONDO:0009276/083/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "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 is absent from gnomAD v4.1.0 (PM2_Supporting).\n", "contributionDate": { "date": "2026/1/20", "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": "CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/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": "2026/1/20", "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/CA354447931/MONDO:0009276/083/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "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 P12 in PMID: 21173099) with this variant had aggregation absent for ristocetin and present for all other agonists as well as less than 10% expression of GPIba and GP9 as measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome. Additionally, the patient had excessive mucocutaneous bleeding which is consistent with Bernard-Soulier syndrome (PP4). \n", "contributionDate": { "date": "2026/1/20", "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": "CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/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": "2026/1/20", "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/CA354447931/MONDO:0009276/083/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "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 two probands with Bernard-Soulier syndrome (PMIDs: 21173099, 32202057 and 29043243). Both probands were homozygous for the variant (1 PM3 point, PM3). \n", "contributionDate": { "date": "2026/1/20", "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": "CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/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": "2026/1/20", "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/CA354447931/MONDO:0009276/083/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "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 in the same codon has been reported in a patient with Bernard-Soulier syndrome; NM_000174.5(GP9):c.284A>C (p.Tyr95Ser)\n\nHowever, this variant has not yet met the criteria to be classified as pathogenic or likely pathogenic by the ClinGen PD VCEP (PM5 not met).", "contributionDate": { "date": "2026/1/20", "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": "CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447931/MONDO:0009276/083/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA354447931/MONDO:0009276/083/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "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 0.814, which is above the ClinGen PD VCEP threshold of ≥0.773 and predicts a damaging effect on function (PP3_Moderate).", "contributionDate": { "date": "2026/1/20", "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": "CA354447931/MONDO:0009276/083/ci/CA354447931/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083/0/1690", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447931/MONDO:0009276/083", "metadata": { "created": "2026-01-20T16:27:58.447Z", "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, 20 Jan 2026 16:27:58 -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": "fc85773b-0c29-4638-9eb9-53a16007d383", "variant": { "@id": "https://reg.genome.network/allele/CA354447931", "id": "CAR:CA354447931", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000174.5:c.284A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000174.5(GP9):c.284A>G (p.Tyr95Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-30T02:02:27.952Z" } }, "status": { "code": 200, "name": "OK" } }