{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/2b735a0b-196c-4f09-9382-c45ed3ab5c39/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/CA8314813/MONDO:0009276/079/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/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": "2025/11/7", "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/CA8314813/MONDO:0009276/079/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8314813/MONDO:0009276/079/ci/CA8314813/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 2 probands with Bernard-Soulier syndrome (PMID: 17083647 and internal lab contributor). These two individuals were both homozygous for the variant (1 point, PM3).", "contributionDate": { "date": "2025/11/7", "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": "CA8314813/MONDO:0009276/079/ci/CA8314813/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/11/7", "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/CA8314813/MONDO:0009276/079/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8314813/MONDO:0009276/079/ci/CA8314813/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": "Surface expression of GP1ba measured by flow cytometry in BHK cells transiently co-transfected with c.667T>G (p.Trp223Gly) variant GP1BA, and wild type GP1BB and GP9 showed decreased expression at trace WT levels, indicating that this variant impacts protein function (PMID: 17083647)(PS3_supporting).\n\n", "contributionDate": { "date": "2025/11/7", "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": "CA8314813/MONDO:0009276/079/ci/CA8314813/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/11/7", "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/CA8314813/MONDO:0009276/079/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8314813/MONDO:0009276/079/ci/CA8314813/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 variant has been reported to segregate in the proband plus 1 additional homozygous BSS affected family members (1 point, PP1, PMID: 17083647).", "contributionDate": { "date": "2025/11/7", "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": "CA8314813/MONDO:0009276/079/ci/CA8314813/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/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": "2025/11/7", "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/CA8314813/MONDO:0009276/079/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8314813/MONDO:0009276/079/ci/CA8314813/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 0.562, which is below the ClinGen PD VCEP PP3 threshold of >0.644 and does not predict a damaging effect on GP1BA function. The computational splicing predictor SpliceAI indicated that the variant has no predicted impact on splicing (Splice AI score <0.5).\n", "contributionDate": { "date": "2025/11/7", "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": "CA8314813/MONDO:0009276/079/ci/CA8314813/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/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": "2025/11/7", "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/CA8314813/MONDO:0009276/079/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8314813/MONDO:0009276/079/ci/CA8314813/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 (Patient 2 in PMID:17083647) with this variant had aggregation absent for ristocetin and present for all other agonists as well as absent expression of GPIba measured by Western blot, 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": "2025/11/7", "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": "CA8314813/MONDO:0009276/079/ci/CA8314813/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/MONDO:0009276/079/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8314813/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": "2025/11/7", "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/CA8314813/MONDO:0009276/079/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8314813/MONDO:0009276/079/ci/CA8314813/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 Grpmax Filtering allele frequency in gnomAD v4.1.0 is 7.900e-7 (based on 4/1179888 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001114; PM2_Supporting).\n", "contributionDate": { "date": "2025/11/7", "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": "CA8314813/MONDO:0009276/079/ci/CA8314813/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8314813/MONDO:0009276/079", "metadata": { "created": "2025-11-07T13:32:57.211Z", "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, 07 Nov 2025 13:32:57 -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": "2b735a0b-196c-4f09-9382-c45ed3ab5c39", "variant": { "@id": "https://reg.genome.network/allele/CA8314813", "id": "CAR:CA8314813", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000173.7:c.667T>G" } ], "preferred": true } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-03T09:56:23.664Z" } }, "status": { "code": 200, "name": "OK" } }