{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/e41b1f54-7b80-4041-a1b3-4a65b690c23a/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 1.1.0", "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/CA2602709/MONDO:0009276/083/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/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": "2026/3/17", "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/CA2602709/MONDO:0009276/083/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602709/MONDO:0009276/083/ci/CA2602709/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 0.619, 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": "2026/3/17", "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": "CA2602709/MONDO:0009276/083/ci/CA2602709/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/MONDO:0009276/083/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/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": "2026/3/17", "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/CA2602709/MONDO:0009276/083/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602709/MONDO:0009276/083/ci/CA2602709/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 BSS8.02 in PMID: 23402648; internal) with this variant had aggregation absent for ristocetin and present for all other agonists and less than 10% expression of GPIba/GP9 measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome (PP4). Additionally, the patient had macrothrombocytopenia which is consistent with Bernard-Soulier syndrome. \n\nOnly sequencing of GP1BA, GP1BB, and GP9 were done in this paper and the internal case. ", "contributionDate": { "date": "2026/3/17", "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": "CA2602709/MONDO:0009276/083/ci/CA2602709/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/MONDO:0009276/083/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/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": "2026/3/17", "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/CA2602709/MONDO:0009276/083/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602709/MONDO:0009276/083/ci/CA2602709/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 0.000001250 (based on 5/1170352 alleles) in the European (non-Finnish) population, which is below the <0.0000329 threshold for PM2_supporting.", "contributionDate": { "date": "2026/3/17", "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": "CA2602709/MONDO:0009276/083/ci/CA2602709/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/MONDO:0009276/083/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/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": "2026/3/17", "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/CA2602709/MONDO:0009276/083/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602709/MONDO:0009276/083/ci/CA2602709/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 0.619, which is above the ClinGen PD VCEP threshold of <0.290", "contributionDate": { "date": "2026/3/17", "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": "CA2602709/MONDO:0009276/083/ci/CA2602709/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/MONDO:0009276/083/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/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": "2026/3/17", "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/CA2602709/MONDO:0009276/083/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602709/MONDO:0009276/083/ci/CA2602709/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 3 probands with Bernard-Soulier syndrome. Two of those individuals were compound heterozygous for this variant and the NM_000174.5(GP9):c.182A>G (p.Asn61Ser) variant which has been classified as Pathogenic by the PD VCEP. The phase of the variants was confirmed to be in trans in one of these patients (Internal from Versiti), but the phase was unknown in the other patient (PMID: 25370924). Additionally, one proband was homozygous for the variant in PMID:23402648 (2 PM3 points, PM3_Strong). \n\n\nVersiti 1: path variant, confirmed in trans = 1 point\nVersiti 2: in trans with lb variant = 0 points\nAli: 23402648 = 0.5\nPMID: 25370924- path variant phase unknown = 0.5 point\n\n", "contributionDate": { "date": "2026/3/17", "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": "CA2602709/MONDO:0009276/083/ci/CA2602709/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/MONDO:0009276/083/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602709/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": "2026/3/17", "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/CA2602709/MONDO:0009276/083/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602709/MONDO:0009276/083/ci/CA2602709/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 variant is present at this codon, NM_000174.5(GP9):c.404G>T (p.Cys135Phe)\n has been classified as VUS by the PD VCEP.", "contributionDate": { "date": "2026/3/17", "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": "CA2602709/MONDO:0009276/083/ci/CA2602709/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602709/MONDO:0009276/083", "metadata": { "created": "2026-03-17T19:18:56.354Z", "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, 17 Mar 2026 19:18:56 -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": "e41b1f54-7b80-4041-a1b3-4a65b690c23a", "variant": { "@id": "https://reg.genome.network/allele/CA2602709", "id": "CAR:CA2602709", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000174.5:c.404G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000174.5:c.404G>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T14:30:34.018Z" } }, "status": { "code": 200, "name": "OK" } }