{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/f7b1c7c0-e94c-4adc-9ff1-69192f1f5cd3/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 1.3.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.3.0" }, "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/CA213771/MONDO:0015967/086/el/0/1837", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/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": "2023/8/13", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0061", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0061", "label": "PP2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA213771/MONDO:0015967/086/ci/CA213771/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": "2023/8/13", "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": "CA213771/MONDO:0015967/086/ci/CA213771/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1837", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/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": "2023/8/13", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic 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provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA213771/MONDO:0015967/086/ci/CA213771/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 v2.1.1 Popmax minor filtering allele frequency due to 0 copies in the European non-Finnish subpopulation and 1 copies in the African/African American subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (ENF Popmax FAF <= 0.000003 and <= 2 copies in ENF and <=1 copy in any other subpopulation) (PM2_Supporting). 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internal lab contributors).", "contributionDate": { "date": "2023/8/13", "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": "CA213771/MONDO:0015967/086/ci/CA213771/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/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": "2023/8/13", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/006", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "006", "label": "PM1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA213771/MONDO:0015967/086/ci/CA213771/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": "2023/8/13", "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": "CA213771/MONDO:0015967/086/ci/CA213771/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2023/8/13", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0023", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0023", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA213771/MONDO:0015967/086/ci/CA213771/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 segregated with diabetes/hyperglycemia with 23 informative meioses in multiple families \n (PP1_Strong; internal lab contributors). ", "contributionDate": { "date": "2023/8/13", "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": "CA213771/MONDO:0015967/086/ci/CA213771/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2023/8/13", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0045", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0045", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA213771/MONDO:0015967/086/ci/CA213771/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": "A kinetic analysis of recombinant wild-type (WT) and mutant glucokinase demonstrated that the wild-type kinetic parameters passed the quality control, the wild-type ATP Km was between 0.4-0.65, the p.Gly72Arg had a relative activity index (RAI) > 0.5 and a relative stability index (RSI) <=0.5 (PS3_Supporting; PMID: 25015100). ", "contributionDate": { "date": "2023/8/13", "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": "CA213771/MONDO:0015967/086/ci/CA213771/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/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": "2023/8/13", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0018", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0018", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA213771/MONDO:0015967/086/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA213771/MONDO:0015967/086/ci/CA213771/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 (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and OGTT increment < 3 mmol/L) (PP4_Moderate, internal lab contributors).", "contributionDate": { "date": "2023/8/13", "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": "CA213771/MONDO:0015967/086/ci/CA213771/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA213771/MONDO:0015967/086", "metadata": { "created": "2024-09-28T02:33:34.604Z", "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": "Sat, 28 Sep 2024 02:33:34 -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": "f7b1c7c0-e94c-4adc-9ff1-69192f1f5cd3", "variant": { "@id": "https://reg.genome.network/allele/CA213771", "id": "CAR:CA213771", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000162.5:c.214G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000162.5(GCK):c.214G>A (p.Gly72Arg)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-04T22:19:24.297Z" } }, "status": { "code": 200, "name": "OK" } }