{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/6fb20210-ced8-47f1-ba35-7a2d754e4145/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "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/CA10360246/MONDO:0100039/016/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2022/9/6", "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/0011", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0011", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2022/9/6", "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": "CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2022/9/6", "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/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "comments": "PMID 28454995: Patient ID:21, affected with infantile epileptic encephalopathy, reported homozygous for the p.L97= variant. Parental testing results not mentioned. Not applying any criteria.\nThe p.Leu97= variant in CDKL5 has been reported apparently homozygous in an individual with infantile epileptic encephalopathy (PMID 28454995); no criteria were applied for this case.", "contributionDate": { "date": "2022/9/6", "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": "CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1633", "type": 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"https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "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.Leu97= variant is observed in at least 2 unaffected individuals (internal database)", "contributionDate": { "date": "2022/9/6", "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": "CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1702/1704", "type": "EvidenceLine" } ], "id": 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"criterion": { "@id": "https://obofoundry.org/sepio/clingen/0087", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000325", "id": "SEPIO:0000325", "label": "Benign Stand Alone" }, "id": "0087", "label": "BA1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2022/9/6", "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": 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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/0070", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0070", "label": "BS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "comments": "The allele frequency of the p.Leu97= variant in CDKL5 is 0.011% in African sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions.", "contributionDate": { "date": "2022/9/6", "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": "CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "contributionDate": { "date": "2022/9/6", "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/0079", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0079", "label": "BP7", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10360246/MONDO:0100039/016/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50022_EP161901869799975", "id": "CG-PCER-AGENT:CG_50022_EP161901869799975", "type": "Agent" }, "comments": "The silent p.Leu97= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide", "contributionDate": { "date": "2022/9/6", "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": "CA10360246/MONDO:0100039/016/ci/CA10360246/MONDO:0100039/016.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016/0/1654", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10360246/MONDO:0100039/016", "metadata": { "created": "2024-09-28T00:32:35.953Z", "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 00:32:35 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6675-8", "id": "LN:LA6675-8", "label": "Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "6fb20210-ced8-47f1-ba35-7a2d754e4145", "variant": { "@id": "https://reg.genome.network/allele/CA10360246", "id": "CAR:CA10360246", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001323289.2:c.291C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001323289.2(CDKL5):c.291C>T (p.Leu97=)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T08:33:26.669Z" } }, "status": { "code": 200, "name": "OK" } }