{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/1d14eddf-504c-4239-b7dd-860bbcd06bdb/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1552193476", "label": "ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100437", "id": "MONDO:0100437", "label": "RPGR-related retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/8/4", "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/CA327916152/MONDO:0100437/106/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "The variant has been reported in a family in which 3 members are affected with retinal dystrophy, however, only the proband has been genotyped, so the PP1 code is not met (PMID: 34745198).", "contributionDate": { "date": "2025/8/4", "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": "CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/8/4", "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/CA327916152/MONDO:0100437/106/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "At least one proband harboring this variant exhibits a phenotype including genetic testing with WES (2 pts), X-linked inheritance (2 pts), early onset (1 pts), night blindness (0.5 pts), reduced visual acuity (0.5 pts), which together are specific for RPGR-related retinopathy (6 points, PP4). However, using this code requires a male, and the proband is a female.", "contributionDate": { "date": "2025/8/4", "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": "CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/8/4", "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/CA327916152/MONDO:0100437/106/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This is a nonsense variant that introduces a premature stop codon between amino acids 1-1132 that is predicted to either trigger nonsense-mediated decay or to disrupt a critical C-terminal region required for proper glutamylation of RPGR (PVS1, PMID: 36445968).", "contributionDate": { "date": "2025/8/4", "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": "CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/8/4", "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/CA327916152/MONDO:0100437/106/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant has been reported in at least 1 proband meeting the PS4 requirement of some functional vision impairment in affected males by age 30, with decreased or absent cone and/or rod ERG responses or a female with functional visual abnormality and documentation of a male relative\naffected with retinitis pigmentosa (PMID: 34745198). However, PS4_Supporting requires at least 2 unrelated probands, so this criterion was not met.", "contributionDate": { "date": "2025/8/4", "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": "CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA327916152/MONDO:0100437/106/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/8/4", "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/CA327916152/MONDO:0100437/106/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/8/4", "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": "CA327916152/MONDO:0100437/106/ci/CA327916152/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA327916152/MONDO:0100437/106", "metadata": { "created": "2025-08-04T04:01:20.208Z", "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, 04 Aug 2025 04:01:20 -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": "1d14eddf-504c-4239-b7dd-860bbcd06bdb", "variant": { "@id": "https://reg.genome.network/allele/CA327916152", "id": "CAR:CA327916152", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001034853.2:c.2248G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001034853.2(RPGR):c.2248G>T (p.Glu750Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T20:56:32.045Z" } }, "status": { "code": 200, "name": "OK" } }