{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/a3fb4056-958f-4d2d-a567-0290d42c1e94/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/CA10581687/MONDO:0100451/226/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/MONDO:0100451/226/ei/1/1652", "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/CA10581687/MONDO:0100451/226/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10581687/MONDO:0100451/226/ci/CA10581687/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 2 unrelated probands with early-onset severe retinal dystrophy who were homozygous for the variant (1 point, PMIDs: 29398085, 28418496). This variant has also been reported in at least 1 proband with early-onset severe retinal dystrophy who was compound heterozygous with the p.Arg1465Ter variant confirmed in trans (1 point, PMID: 29398085), which was previously classified pathogenic by the ClinGen LCA/eoRD VCEP (2 total points, PM3_Strong).\n", "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": "CA10581687/MONDO:0100451/226/ci/CA10581687/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/MONDO:0100451/226/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/MONDO:0100451/226/ei/1/1649", "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/CA10581687/MONDO:0100451/226/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10581687/MONDO:0100451/226/ci/CA10581687/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 at least 4 similarly affected relatives, with the variant present in the compound heterozygous state (PMID:29298085) and in a family with 3 homozygous siblings (PMID:28418496) (PP1_Strong).\n", "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": "CA10581687/MONDO:0100451/226/ci/CA10581687/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/MONDO:0100451/226/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/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/CA10581687/MONDO:0100451/226/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10581687/MONDO:0100451/226/ci/CA10581687/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 25.9, which is above the ClinGen LCA/eoRD VCEP threshold of ≥25.3 and predicts a damaging effect on CEP290 protein function (PP3). The splicing impact predictor SpliceAI gives a score of 0.08 for acceptor loss, which is below the ClinGen LCA/eoRD VCEP recommended threshold of ≥0.2 and does not predict a deleterious 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": "CA10581687/MONDO:0100451/226/ci/CA10581687/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/MONDO:0100451/226/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/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/CA10581687/MONDO:0100451/226/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10581687/MONDO:0100451/226/ci/CA10581687/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 a diagnosis of LCA (0.5 pts), symptoms present from birth (0.5 pts), severely reduced visual acuity (0.5 pts) and no clear progression in first decade (0.5 pts). Vision was worse under bright light (0.5 pts), night vision always impaired (0.5 pts). Fundi showed widespread outer retinal atrophy with relative sparing of the macula (1 pt). OCT showed only a small region of preservation of the photoreceptor layers. Together these are specific for CEP290-related ciliopathy (total 4 points, PMID: 29398085 and additional details from coauthor, PP4).", "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": "CA10581687/MONDO:0100451/226/ci/CA10581687/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/MONDO:0100451/226/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10581687/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/CA10581687/MONDO:0100451/226/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10581687/MONDO:0100451/226/ci/CA10581687/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 absent from gnomAD v4.1.0 (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": "CA10581687/MONDO:0100451/226/ci/CA10581687/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10581687/MONDO:0100451/226", "metadata": { "created": "2026-07-20T16:23:02.584Z", "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 16:23:02 -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": "a3fb4056-958f-4d2d-a567-0290d42c1e94", "variant": { "@id": "https://reg.genome.network/allele/CA10581687", "id": "CAR:CA10581687", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_025114.4:c.148C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_025114.4(CEP290):c.148C>T (p.His50Tyr)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-03T23:36:22.460Z" } }, "status": { "code": 200, "name": "OK" } }