{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/878639da-2681-4ca3-968e-76c232e46fac/doc/sepio/version/1.1.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528339111", "label": "ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 3.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "3.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015967", "id": "MONDO:0015967", "label": "monogenic diabetes", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant was identified in five unrelated individuals with hyperglycemia (PS4_Moderate; PMIDs: 19790256, 34440516, 36178555; internal lab contributors).", "contributionDate": { "date": "2025/9/8", "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": "CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/el/0/1774", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1775", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1774/1776", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "Another missense variant, c.821A>C p.(Asp274Ala), has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.(Asp274Glu) (PM5_Supporting).", "contributionDate": { "date": "2025/9/8", "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": "CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1774/1776", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/1/1775", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1774", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (fasting glucose 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and negative antibodies) (PP4_Moderate; PMID: 36178555, internal lab contributors). 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"https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1838", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2).", "contributionDate": { "date": "2025/9/8", "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": "CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1837", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.929, which is greater than the MDEP VCEP threshold of 0.70 (PP3).", "contributionDate": { "date": "2025/9/8", "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": "CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to the presence of only 1 copy in any subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (Grpmax FAF less than or equal to 0.000003) (PM2_Supporting). ", "contributionDate": { "date": "2025/9/8", "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": "CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367400482/MONDO:0015967/086/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA367400482/MONDO:0015967/086/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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": "CA367400482/MONDO:0015967/086/ci/CA367400482/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086/0/1615", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367400482/MONDO:0015967/086", "metadata": { "created": "2025-09-08T21:10:44.349Z", "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": "Mon, 08 Sep 2025 21:10:44 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "878639da-2681-4ca3-968e-76c232e46fac", "variant": { "@id": "https://reg.genome.network/allele/CA367400482", "id": "CAR:CA367400482", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000162.5:c.822C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000162.5(GCK):c.822C>A (p.Asp274Glu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T07:33:23.748Z" } }, "status": { "code": 200, "name": "OK" } }