{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/315ba369-6ff6-45a0-b82a-1532bf01de7f/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/CA116663/MONDO:0009276/079/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/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": "2025/9/4", "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/CA116663/MONDO:0009276/079/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA116663/MONDO:0009276/079/ci/CA116663/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 (Kalstad homozygote in PMID:25370924) with this variant had absent (< 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 and macrothrombocytopenia which are consistent with Bernard-Soulier syndrome (PP4).", "contributionDate": { "date": "2025/9/4", "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": "CA116663/MONDO:0009276/079/ci/CA116663/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/MONDO:0009276/079/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/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": "2025/9/4", "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/CA116663/MONDO:0009276/079/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA116663/MONDO:0009276/079/ci/CA116663/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 0.000009540 (based on 18/1179684 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001114; PM2_Supporting).", "contributionDate": { "date": "2025/9/4", "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": "CA116663/MONDO:0009276/079/ci/CA116663/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/MONDO:0009276/079/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/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": "2025/9/4", "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/CA116663/MONDO:0009276/079/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA116663/MONDO:0009276/079/ci/CA116663/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.1620G>A (p.Trp540Ter) variant in GP1BA is a nonsense variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay. However the truncation includes the functionally important transmembrane domain (removes amino acids 540-553) in a gene where loss-of-function is an established disease mechanism (PVS1_Strong; PMID:9639514).\n", "contributionDate": { "date": "2025/9/4", "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": "CA116663/MONDO:0009276/079/ci/CA116663/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/MONDO:0009276/079/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/MONDO:0009276/079/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/9/4", "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/CA116663/MONDO:0009276/079/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA116663/MONDO:0009276/079/ci/CA116663/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 a homozygous proband plus 2 compound heterozygotes and 7 additional heterozygous relatives with macrothrombocytopenia that were not scored due to lack of data for each heterozygote (2 points: PMID:25370924). The variant has also been reported to segregate in a proband plus 1 additional compound heterozygous BSS affected sibling (1 point: PMID: 9639514). Total segregation pts: 3 pts.", "contributionDate": { "date": "2025/9/4", "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": "CA116663/MONDO:0009276/079/ci/CA116663/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/MONDO:0009276/079/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/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": "2025/9/4", "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/CA116663/MONDO:0009276/079/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA116663/MONDO:0009276/079/ci/CA116663/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 5 probands with Bernard-Soulier syndrome. Two of those individuals were homozygous for this variant (1 point). Two probands were compound homozygous for this variant and the p.Cys81Arg variant and confirmed in trans by family testing, but was used for the p.Cys81Arg curation so not used for this curation (0 points). Another proband (different publication and authorship) was compound homozygous for this variant and the p.Cys81Arg variant and confirmed in trans by family testing, but was used for this curation and not used for the p.Cys81Arg curation (1 point). Total points: 2 (PM3).", "contributionDate": { "date": "2025/9/4", "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": "CA116663/MONDO:0009276/079/ci/CA116663/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/MONDO:0009276/079/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA116663/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": "2025/9/4", "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/CA116663/MONDO:0009276/079/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA116663/MONDO:0009276/079/ci/CA116663/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 GP1a measured by flow cytometry in CHO cells transiently co-transfected with the p.Trp540Ter variant in GP1a and wild type GP1b, and GP9 was barely detectable compared to controls, indicating that this variant impacts protein function (PMID:9639514)(PS3_supporting).", "contributionDate": { "date": "2025/9/4", "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": "CA116663/MONDO:0009276/079/ci/CA116663/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079/0/1696", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA116663/MONDO:0009276/079", "metadata": { "created": "2025-09-04T21:42:43.678Z", "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, 04 Sep 2025 21:42:43 -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": "315ba369-6ff6-45a0-b82a-1532bf01de7f", "variant": { "@id": "https://reg.genome.network/allele/CA116663", "id": "CAR:CA116663", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000173.7:c.1620G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000173.7(GP1BA):c.1620G>A (p.Trp540Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T22:30:20.333Z" } }, "status": { "code": 200, "name": "OK" } }