{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/f7b48811-99dd-4607-bc7c-cff00d6c20db/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/CA2602698/MONDO:0009276/083/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/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": "2025/3/6", "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/CA2602698/MONDO:0009276/083/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602698/MONDO:0009276/083/ci/CA2602698/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 0.196, which is below the ClinGen PD VCEP threshold of <0.290 and predicts no damaging effect on GP9 function and the computational splicing predictor SpliceAI reported a delta score 0.01 for acceptor gain (BP4_NotMet) ", "contributionDate": { "date": "2025/3/6", "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": "CA2602698/MONDO:0009276/083/ci/CA2602698/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/MONDO:0009276/083/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/MONDO:0009276/083/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/3/6", "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/CA2602698/MONDO:0009276/083/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602698/MONDO:0009276/083/ci/CA2602698/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 gnomAD v4.1 is 0.001561 (based on 1906/1175218 alleles) in the European (non-Finnish) population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets this criterion (BA1).", "contributionDate": { "date": "2025/3/6", "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": "CA2602698/MONDO:0009276/083/ci/CA2602698/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/MONDO:0009276/083/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/MONDO:0009276/083/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/3/6", "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/CA2602698/MONDO:0009276/083/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602698/MONDO:0009276/083/ci/CA2602698/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": "Internal cases: found this variant in heterozygosis in four cases in IPD series. All four have moderate macrothrombocytopenia\n\nnot considered due to high allele frequency and no PP4 meeting BSS patient", "contributionDate": { "date": "2025/3/6", "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": "CA2602698/MONDO:0009276/083/ci/CA2602698/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/MONDO:0009276/083/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2602698/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": "2025/3/6", "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/CA2602698/MONDO:0009276/083/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2602698/MONDO:0009276/083/ci/CA2602698/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": "PMID: 28561420. Report of two neonates heterozygous for the variant with severe neonatal thrombocytopenia and life-threatening intra-cranial hemorrhage. This was attributed to the variant causing a new alloantigen that was incompatible with their mother. Mother was homozygous for the wild-type allele and father was heterozygous for the variant. Does not meet PP4. \n\nPMID: 28748566. Variant found in patient #24 (see table S2). Does not meet PP4, more details/specifics needed about clinical phenotype of patient.\n\nInternal cases: found this variant in heterozygosis in four cases in IPD series. All four have moderate macrotrombocytopenia", "contributionDate": { "date": "2025/3/6", "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": "CA2602698/MONDO:0009276/083/ci/CA2602698/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083/0/1633", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2602698/MONDO:0009276/083", "metadata": { "created": "2025-03-06T22:19:27.290Z", "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, 06 Mar 2025 22:19:26 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6675-8", "id": "LN:LA6675-8", "label": "Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "f7b48811-99dd-4607-bc7c-cff00d6c20db", "variant": { "@id": "https://reg.genome.network/allele/CA2602698", "id": "CAR:CA2602698", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000174.5:c.368C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000174.5(GP9):c.368C>T (p.Pro123Leu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-08T18:31:21.167Z" } }, "status": { "code": 200, "name": "OK" } }