{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/f8c0d4cf-55cb-4f31-83a8-a2327d7176dd/doc/sepio/version/1.0.0", "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 3.1", "type": "VariantPathogenicityInterpretationGuideline", "version": "3.1" }, "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/CA367401938/MONDO:0015967/086/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/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": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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 no copies in the European non-Finnish subpopulation and one copy in any other subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (Grpmax FAF <= 0.000003 and <= 2 copies in ENF and <=1 copy in any other subpopulation) (PM2_Supporting). ", "contributionDate": { "date": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/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": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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 four unrelated individuals with hyperglycemia (PS4_Moderate; PMID: 19564454, 36257325, internal lab contributors).", "contributionDate": { "date": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/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": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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 antibody) (PP4_Moderate; internal lab contributors). ", "contributionDate": { "date": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/el/0/1603", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/ei/1/1604", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1603/1605", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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 as a de novo occurrence with unconfirmed parental relationships in an individual with hyperglycemia, but with insufficient clinical information to determine if the phenotype is highly specific for GCK-hyperglycemia (PS2_Supporting; internal lab contributors).", "contributionDate": { "date": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1603/1605", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1604", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1603", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/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": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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 resides in an amino acid that directly binds glucose, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1).", "contributionDate": { "date": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/el/0/1837", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/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": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1837", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/MONDO:0015967/086/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367401938/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": "2026/7/30", "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/CA367401938/MONDO:0015967/086/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367401938/MONDO:0015967/086/ci/CA367401938/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 0.991, which is greater than the MDEP VCEP threshold of 0.70 (PP3).", "contributionDate": { "date": "2026/7/30", "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": "CA367401938/MONDO:0015967/086/ci/CA367401938/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086/0/1747", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367401938/MONDO:0015967/086", "metadata": { "created": "2026-07-30T13:44:41.467Z", "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, 30 Jul 2026 13:44:41 -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": "f8c0d4cf-55cb-4f31-83a8-a2327d7176dd", "variant": { "@id": "https://reg.genome.network/allele/CA367401938", "id": "CAR:CA367401938", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000162.5:c.451T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000162.5(GCK):c.451T>C (p.Ser151Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T09:52:36.142Z" } }, "status": { "code": 200, "name": "OK" } }