{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/0ff7deb4-f87f-4d5e-95c1-a7ad1a5bfa8d/doc/sepio/version/1.1.0", "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 1.1.0", "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/CA2602666/MONDO:0009276/083/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/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": "2026/1/23", "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/CA2602666/MONDO:0009276/083/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602666/MONDO:0009276/083/ci/CA2602666/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 0.623, which is below the ClinGen PD VCEP PP3 threshold of >0.644 and does not predict a damaging effect on GP9 function. And the computational splicing predictor SpliceAI indicated that the variant has no predicted impact on splicing.", "contributionDate": { "date": "2026/1/23", "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": "CA2602666/MONDO:0009276/083/ci/CA2602666/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/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": "2026/1/23", "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/CA2602666/MONDO:0009276/083/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602666/MONDO:0009276/083/ci/CA2602666/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 BS-23 in PMID:21699652) with this variant had aggregation absent for ristocetin and present for all other agonists, as well as 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 is consistent with Bernard-Soulier syndrome (PP4). ", "contributionDate": { "date": "2026/1/23", "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": "CA2602666/MONDO:0009276/083/ci/CA2602666/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/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": "2026/1/23", "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/CA2602666/MONDO:0009276/083/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602666/MONDO:0009276/083/ci/CA2602666/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 Grpmax filtering allele frequency in gnomaDv4.1 is 0 (based on 1/1179890 alleles) in the European (non-Finnish) population, which is below the <0.0000329 threshold for PM2_supporting.", "contributionDate": { "date": "2026/1/23", "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": "CA2602666/MONDO:0009276/083/ci/CA2602666/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2026/1/23", "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/CA2602666/MONDO:0009276/083/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602666/MONDO:0009276/083/ci/CA2602666/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 0.623, which is above the ClinGen PD VCEP PP3 threshold of <0.290.", "contributionDate": { "date": "2026/1/23", "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": "CA2602666/MONDO:0009276/083/ci/CA2602666/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2026/1/23", "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/CA2602666/MONDO:0009276/083/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602666/MONDO:0009276/083/ci/CA2602666/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 three unrelated probands with Bernard-Soulier syndrome. Two of these individuals were homozygous for the variant (PMID:21699652, 1 PM3 point). One individual was compound heterozygous for this variant and the NM_000174.5(GP9):c.182A>G (p.Asn61Ser) which has been classified as Pathogenic by the PD VCEP. (1 PM3 point). These variants were confirmed in trans by family testing (2 PM3 points, PM3_Strong). \n\n\n\n", "contributionDate": { "date": "2026/1/23", "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": "CA2602666/MONDO:0009276/083/ci/CA2602666/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/MONDO:0009276/083/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602666/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": "2026/1/23", "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/CA2602666/MONDO:0009276/083/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602666/MONDO:0009276/083/ci/CA2602666/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 c.212T>C (p.Phe71Ser) classified as likely pathogenic by the ClinGen PD VCEP, not considered here to avoid circularity.", "contributionDate": { "date": "2026/1/23", "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": "CA2602666/MONDO:0009276/083/ci/CA2602666/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602666/MONDO:0009276/083", "metadata": { "created": "2026-01-23T14:46:49.742Z", "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, 23 Jan 2026 14:46:49 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "0ff7deb4-f87f-4d5e-95c1-a7ad1a5bfa8d", "variant": { "@id": "https://reg.genome.network/allele/CA2602666", "id": "CAR:CA2602666", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000174.5:c.212T>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000174.5(GP9):c.212T>G (p.Phe71Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T15:08:19.112Z" } }, "status": { "code": 200, "name": "OK" } }