{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/c6bead1b-4767-4da6-9897-aef4e49f0777/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/CA6711610/MONDO:0100451/226/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/ei/1/1805", "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/CA6711610/MONDO:0100451/226/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA6711610/MONDO:0100451/226/ci/CA6711610/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 v4.1.1 at a Grpmax allele frequency of 0.001149, with 12 alleles / 6,020 total alleles in the Middle Eastern population, which is lower than the ClinGen LCA/eoRD VCEP BS1 threshold of >0.0016.", "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": "CA6711610/MONDO:0100451/226/ci/CA6711610/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/el/0/1579", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/ei/1/1580", "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/CA6711610/MONDO:0100451/226/el/0/1579/1581", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA6711610/MONDO:0100451/226/ci/CA6711610/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 in at least 1 proband with a severe sperm motility disorder who harbored the variant in the compound heterozygous state and also harbored homozygous missense variants in several other candidate genes, however, the proband was not counted for BP5 because sufficient phenotype details were not reported and because this code is considered not applicable to CEP290 due to the high genetic heterogeneity and limited phenotypic specificities of retinal dystrophies (PMID: 34089056).", "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": "CA6711610/MONDO:0100451/226/ci/CA6711610/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1579", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/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/CA6711610/MONDO:0100451/226/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA6711610/MONDO:0100451/226/ci/CA6711610/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 renal anomalies and renal disease who harbored the variant in the compound heterozygous state, however, the proband was not counted for PM3 because sufficient phenotype details were not reported and because the NM_025114.4(CEP290):c.963T>A (p.Asp321Glu) variant suspected in trans has been classified as a VUS (PMID: 40718208). The variant has also been reported in at least 1 proband with a severe sperm motility disorder who harbored the variant in the compound heterozygous state, however, the proband was not counted for PM3 because sufficient details were not reported and because the NM_025114.4(CEP290):c.1092T>G (p.Ile364Met) variant suspected in trans has been classified as likely benign.", "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": "CA6711610/MONDO:0100451/226/ci/CA6711610/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/ei/1/1685", "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/CA6711610/MONDO:0100451/226/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA6711610/MONDO:0100451/226/ci/CA6711610/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 PHRED score of 12.9, which is below the ClinGen LCA/eoRD VCEP threshold of <17.3 and predicts a non-damaging effect on CEP290 protein function. In addition, the splicing impact predictor SpliceAI gives a delta score of 0.00 for all splicing events, which is below the ClinGen LCA/eoRD VCEP recommended threshold of ≤0.1 and does not predict an impact on splicing (BP4).", "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": "CA6711610/MONDO:0100451/226/ci/CA6711610/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/MONDO:0100451/226/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA6711610/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/CA6711610/MONDO:0100451/226/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA6711610/MONDO:0100451/226/ci/CA6711610/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 v4.1.1 at a total allele frequency of 0.0001209, with 194 alleles / 1,604,948 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": "CA6711610/MONDO:0100451/226/ci/CA6711610/MONDO:0100451/226.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA6711610/MONDO:0100451/226", "metadata": { "created": "2026-07-20T19:40:20.243Z", "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 19:40:16 -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": "c6bead1b-4767-4da6-9897-aef4e49f0777", "variant": { "@id": "https://reg.genome.network/allele/CA6711610", "id": "CAR:CA6711610", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_025114.4:c.5998A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_025114.4(CEP290):c.5998A>G (p.Ile2000Val)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T00:18:24.197Z" } }, "status": { "code": 200, "name": "OK" } }