{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/ed12e4e0-a9f1-4f0b-858b-8eda63ce5c01/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1565017043", "label": "ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DCLRE1C Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0011225", "id": "MONDO:0011225", "label": "severe combined immunodeficiency due to DCLRE1C deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/1/23", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "The filtering allele frequency (the upper threshold of the 95% CI of 2/1111892 alleles) of the c.95C>T variant in DCLRE1C is 0.0000003 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).", "contributionDate": { "date": "2024/1/23", "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": "CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/ei/1/1826", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/1/23", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0039", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0039", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "Activity levels in % of WT activity = Recombination: Mean (SD): 5.14\t(0.34) and DNA repair (36h after IR): Mean (SD): 20.95 (6.17). Both values are lower than our established threshold for abnormal results (defined as <25% of wild-type activity). Thus, PS3 is Met at a moderate level (PMID: 25917813).\n\n", "contributionDate": { "date": "2024/1/23", "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": "CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/1/23", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "At least one patient in the literature present: Diagnostic criteria for SCID/Leaky SCID/Omenn syndrome met 0.5 pts + T-B-NK+ lymphocyte subset profile 0.5 pts, total 1 pt; Which is highly specific for SCID. PP4_Supporting (PMIDs: 18223550 and 25917813 - same patient).", "contributionDate": { "date": "2024/1/23", "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": "CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/1/23", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "Proband is compound heterozygous, in trans, for del Ex1-3 (at least LP according to our SCID VCEP specifications;) 1 point, PM3_Moderate. (PMID: 25917813).", "contributionDate": { "date": "2024/1/23", "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": "CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/1/23", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA203404964/MONDO:0011225/116/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "NM_001033855.3(DCLRE1C):c.95C>G (p.Ser32Cys) is VUS. Not used here to avoid circularity.", "contributionDate": { "date": "2024/1/23", "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": "CA203404964/MONDO:0011225/116/ci/CA203404964/MONDO:0011225/116.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA203404964/MONDO:0011225/116", "metadata": { "created": "2024-09-28T03:48:01.572Z", "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": "Sat, 28 Sep 2024 03:48:01 -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": "ed12e4e0-a9f1-4f0b-858b-8eda63ce5c01", "variant": { "@id": "https://reg.genome.network/allele/CA203404964", "id": "CAR:CA203404964", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001033855.3:c.95C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001033855.3(DCLRE1C):c.95C>T (p.Ser32Phe)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-05-09T16:01:54.200Z" } }, "status": { "code": 200, "name": "OK" } }