{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/57abb096-4a3b-4e54-b774-0e897a8bd09d/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/485570930", "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CEP290 Version 1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100451", "id": "MONDO:0100451", "label": "CEP290-related ciliopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2026/7/20", "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/CA385979889/MONDO:0100451/226/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "The variant has been reported to segregate with childhood-onset severe retinal dystrophy through the proband plus 1 similarly affected relative, with the variant present in the compound heterozygous state (PMID: 34196655, PP1).", "contributionDate": { "date": "2026/7/20", "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": "CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2026/7/20", "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/CA385979889/MONDO:0100451/226/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "The computational predictor CADD gives a score of 26.5, which is above the ClinGen LCA/eoRD VCEP threshold of ≥25.3 and predicts a damaging effect on CEP290 protein function (PP3). Additionally, the splicing impact predictor SpliceAI gives a score of 0.01 for donor loss, which is below the ClinGen LCA/eoRD VCEP recommended threshold of ≥0.2 and does not strongly predict an impact on splicing.", "contributionDate": { "date": "2026/7/20", "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": "CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2026/7/20", "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/CA385979889/MONDO:0100451/226/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "At least one proband harboring this variant exhibits a phenotype including diagnosis of either Leber congenital amaurosis, early onset severe retinal dystrophy, or retinitis pigmentosa (0.5 pts), which is not sufficiently specific for CEP290-related ciliopathy to meet the PP4 code (0.5 total points, PMID: 34196655).", "contributionDate": { "date": "2026/7/20", "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": "CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2026/7/20", "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/CA385979889/MONDO:0100451/226/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who was compound heterozygous with the NM_025114.4(CEP290):c.1666del (p.Ile556fs) variant confirmed in trans, which was previously classified pathogenic by the ClinGen LCA/eoRD VCEP (1 total point, PMID: 34196655, PM3).", "contributionDate": { "date": "2026/7/20", "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": "CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA385979889/MONDO:0100451/226/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2026/7/20", "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/CA385979889/MONDO:0100451/226/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant is present in gnomAD v4.1.0 at a total allele frequency of 0.0000006505, with 1 allele / 1,537,272 total alleles, which is lower than the ClinGen LCA/eoRD VCEP PM2_Supporting threshold of <0.0006 (PM2_Supporting).", "contributionDate": { "date": "2026/7/20", "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": "CA385979889/MONDO:0100451/226/ci/CA385979889/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA385979889/MONDO:0100451/226", "metadata": { "created": "2026-07-20T21:45:24.568Z", "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, 20 Jul 2026 21:45:24 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "57abb096-4a3b-4e54-b774-0e897a8bd09d", "variant": { "@id": "https://reg.genome.network/allele/CA385979889", "id": "CAR:CA385979889", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_025114.4:c.1466T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_025114.4(CEP290):c.1466T>C (p.Leu489Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T04:06:39.417Z" } }, "status": { "code": 200, "name": "OK" } }