{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/cf0c7138-8040-43a6-a6f2-a97125094a35/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/CA287215802/MONDO:0009276/079/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/ei/1/1616", "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/CA287215802/MONDO:0009276/079/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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": "Not in a hotspot or critical region as determined by the PD VCEP", "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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/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": "2025/9/4", "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/CA287215802/MONDO:0009276/079/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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 0.321, which is below the ClinGen PD VCEP PP3 threshold of >0.644 and does not predict a damaging effect on GP1BA function. And the computational splicing predictor SpliceAI indicated that the variant has no predicted impact on splicing (Splice AI score <0.5).", "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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/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/CA287215802/MONDO:0009276/079/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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 (PMID:25370924, 9639514) with this variant had aggregation absent for ristocetin and present for all other agonists and less than 10% expression of GPIba measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome (PP4).\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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/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/CA287215802/MONDO:0009276/079/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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 is absent from gnomAD v4.1.0 (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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/ei/1/1829", "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/CA287215802/MONDO:0009276/079/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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 demonstrates increased expression of GPIba compared to controls when transfected into CHO cells. vWF binding was absent (PS3 Not Met, PMID:9639514). ", "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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/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": "2025/9/4", "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/CA287215802/MONDO:0009276/079/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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 9 individuals with Bernard-Soulier syndrome. 1 proband was homozygous for the variant (0.5 points). The other homozygotes were not counted assuming there were possibly related to this individual. There were two additional probands that were compound heterozygotes for this variant and a second pathogenic variant, NM_000173.7(GP1BA):c.1620G>A (p.Trp540Ter) with phase confirmed (2 pts). Total points: 2.5.\n\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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/MONDO:0009276/079/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA287215802/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/CA287215802/MONDO:0009276/079/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA287215802/MONDO:0009276/079/ci/CA287215802/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 6 additional homozygous BSS affected individuals from a small town in Iceland and 14 additional heterozygous relatives with low platelet count and larger platelet size (median 9.7 fL) compared to controls (p<0.001 for both comparisons). 9.5 pts total (PP1_strong).", "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": "CA287215802/MONDO:0009276/079/ci/CA287215802/MONDO:0009276/079.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079/0/1648", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA287215802/MONDO:0009276/079", "metadata": { "created": "2025-09-04T22:09:07.988Z", "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 22:09:07 -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": "cf0c7138-8040-43a6-a6f2-a97125094a35", "variant": { "@id": "https://reg.genome.network/allele/CA287215802", "id": "CAR:CA287215802", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000173.7:c.241T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000173.7(GP1BA):c.241T>C (p.Cys81Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T19:18:55.302Z" } }, "status": { "code": 200, "name": "OK" } }