{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/f17498da-243a-4e33-ad83-e4a729eca450/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 1.0.0", "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/CA8315002/MONDO:0009276/079/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/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": "2025/2/13", "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/CA8315002/MONDO:0009276/079/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8315002/MONDO:0009276/079/ci/CA8315002/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 is 0.000004440 (based on 2/74766) in the African/African American population, below the <0.0001114 threshold for PM2_supporting", "contributionDate": { "date": "2025/2/13", "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": "CA8315002/MONDO:0009276/079/ci/CA8315002/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/ei/1/1763", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/13", "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/CA8315002/MONDO:0009276/079/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8315002/MONDO:0009276/079/ci/CA8315002/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 c.1454dup (p.Ser486IlefsTer12) variant in GP1BA is a frameshift variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove 24% (>10%) of the protein (PVS1_Strong).", "contributionDate": { "date": "2025/2/13", "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": "CA8315002/MONDO:0009276/079/ci/CA8315002/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/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": "2025/2/13", "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/CA8315002/MONDO:0009276/079/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8315002/MONDO:0009276/079/ci/CA8315002/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": "Case 2 of PMID: 9241731 is compound heterozygous for the maternal c.1480del (classified Pathogenic by the PD-VCEP) and paternal c.1454dup. (1pt; PM3)\n\nPMID: 11776304 Patient is compound heterozygous for the maternal c.1454dupl and paternal Cys225Ser (classified Pathogenic by the PD-VCEP) variants. Not considered here to avoid circularity.\n\n BSS7.01 from PMID: 23402648: Patient is homozygous for the c.1454dup variant (.5 points).\n\nPatient from PMID:16916536: Patient is homozygous for the c.1454dup variant (.5 points).", "contributionDate": { "date": "2025/2/13", "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": "CA8315002/MONDO:0009276/079/ci/CA8315002/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/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": "2025/2/13", "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/CA8315002/MONDO:0009276/079/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8315002/MONDO:0009276/079/ci/CA8315002/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 GP1Balpha measured by flow cytometry from transient transfection of the c.1454dup variant in CHO cells stably co-expressing the GPIbbeta and GPIX subunits showed decreased expression at 0% (<25%) WT levels, indicating that this variant impacts protein function (PMID:11776304; PS3_supporting).", "contributionDate": { "date": "2025/2/13", "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": "CA8315002/MONDO:0009276/079/ci/CA8315002/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/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": "2025/2/13", "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/CA8315002/MONDO:0009276/079/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8315002/MONDO:0009276/079/ci/CA8315002/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 with Bernard-Soulier syndrome in the proband (meeting PP4) plus one affected family member, both with the compound heterozygous genotype with c.673T>A and c.1454dup variant(s). (PP1; PMID:11776304).", "contributionDate": { "date": "2025/2/13", "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": "CA8315002/MONDO:0009276/079/ci/CA8315002/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/MONDO:0009276/079/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8315002/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": "2025/2/13", "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/CA8315002/MONDO:0009276/079/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8315002/MONDO:0009276/079/ci/CA8315002/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 (Proband in PMID:11776304) with this variant had aggregation absent for ristocetin and present for all other agonists AND flow cytometry with less than 10% expression of GPIba, which is highly specific for Bernard-Soulier syndrome (PP4). Additionally, the patient had excessive mucocutaneous bleeding and macrothrombocytopenia which are consistent with Bernard-Soulier syndrome.", "contributionDate": { "date": "2025/2/13", "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": "CA8315002/MONDO:0009276/079/ci/CA8315002/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079/0/1633", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8315002/MONDO:0009276/079", "metadata": { "created": "2025-02-14T21:36:18.154Z", "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, 14 Feb 2025 21:36:18 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "f17498da-243a-4e33-ad83-e4a729eca450", "variant": { "@id": "https://reg.genome.network/allele/CA8315002", "id": "CAR:CA8315002", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000173.7:c.1454dup" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000173.7:c.1454dup" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T11:11:46.798Z" } }, "status": { "code": 200, "name": "OK" } }