{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d8e89261-2759-41e2-98f7-b0266448c3bc/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243104", "label": "ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDKL5 Version 6.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "6.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100039", "id": "MONDO:0100039", "label": "CDKL5 disorder", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1663", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/ei/1/1664", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2026/9/24", "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/0051", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0051", "label": "PS2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "comments": "The p.Tyr24Cys variant in CDKL5 has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in 2 individuals with clinical features of CDKL5 disorder (internal database - GeneDx; internal database - Variantyx) (PS2). 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", "contributionDate": { "date": "2026/9/24", "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": "CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2026/9/24", "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/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2026/9/24", "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": "CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2026/9/24", "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 Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "comments": "Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).", "contributionDate": { "date": "2026/9/24", "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": "CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412489792/MONDO:0100039/034/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2026/9/24", "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/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/CA412489792/MONDO:0100039/034/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "comments": "The p.Tyr24Cys variant in CDKL5 is absent from gnomAD v4.1 (PM2_Supporting).", "contributionDate": { "date": "2026/9/24", "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": "CA412489792/MONDO:0100039/034/ci/CA412489792/MONDO:0100039/034.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412489792/MONDO:0100039/034", "metadata": { "created": "2026-10-15T19:03:50.491Z", "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, 15 Oct 2026 19:03:50 -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": "d8e89261-2759-41e2-98f7-b0266448c3bc", "variant": { "@id": "https://reg.genome.network/allele/CA412489792", "id": "CAR:CA412489792", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001323289.2:c.71A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001323289.2(CDKL5):c.71A>G (p.Tyr24Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T10:05:23.292Z" } }, "status": { "code": 200, "name": "OK" } }