{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/2d299d0b-fbf5-47cc-84f6-ba333a419de9/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1733815116", "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GUCY2D Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100453", "id": "MONDO:0100453", "label": "GUCY2D-related recessive retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA8366018/MONDO:0100453/167/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "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 LCA (0.5), present at birth (1 pt.), visual acuity of LP (light perception) (1 pt), visual field loss (1 pt), nystagmus (1 pt), photophobia (1 pt), non-recordable ERGs (1.5 pts), and without alternative variants after large gene panel testing (2 pts). Together these are highly specific for GUCY2D-related recessive retinopathy (total 9 points, PMID: 23847139, PP4_Moderate).", "contributionDate": { "date": "2025/1/30", "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": "CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/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": "2025/1/30", "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/CA8366018/MONDO:0100453/167/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "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 v.4.1.0 at a total allele frequency of 0.000006199, with 10 alleles / 1,613,180 total alleles, which is lower than the ClinGen LCA/eoRD VCEP PM2_Supporting threshold of <0.0004 (PM2_Supporting).\n", "contributionDate": { "date": "2025/1/30", "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": "CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA8366018/MONDO:0100453/167/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "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 REVEL gives a score of 0.857, which is above the ClinGen LCA / eoRD VCEP threshold of ≥0.773 and predicts a damaging effect on RetGC-1 function (PP3_Moderate).", "contributionDate": { "date": "2025/1/30", "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": "CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8366018/MONDO:0100453/167/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA8366018/MONDO:0100453/167/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "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 one proband with early-onset severe retinal dystrophy who was homozygous for the variant (0.5 points, PMID: 23847139). This variant has also been reported in one proband with early-onset severe retinal dystrophy who was compound heterozygous with the p.Glu196Val variant suspected in trans (0 points, PMID:20683928), which has not been classified by the ClinGen LCA / eoRD VCEP (0.5 total points, PM3_Supporting).", "contributionDate": { "date": "2025/1/30", "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": "CA8366018/MONDO:0100453/167/ci/CA8366018/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8366018/MONDO:0100453/167", "metadata": { "created": "2025-01-30T17:31:06.930Z", "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, 30 Jan 2025 17:31:06 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "2d299d0b-fbf5-47cc-84f6-ba333a419de9", "variant": { "@id": "https://reg.genome.network/allele/CA8366018", "id": "CAR:CA8366018", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000180.4:c.2132C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000180.4(GUCY2D):c.2132C>T (p.Pro711Leu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T12:16:52.594Z" } }, "status": { "code": 200, "name": "OK" } }