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} ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "This variant does not reside within a region of the RNAse IIIb domain that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP (PM1 not met).\n", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "Another missense variant c.2516C>G (p.Ser839Cys) with Grantham score equal to or less than the current variant has been reported in the same codon (ClinVar Variation ID: 935119). However, this variant has not yet met the criteria to be classified as pathogenic by the ClinGen DICER1 VCEP (PM5 not met).", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.519, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function; splice predictors MaxEntScan and SpliceAI indicate no impact on splicing (PP3 and BP4 not met).", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "At least one patient with this variant was found to have a somatic second hit in a recognized DICER1 hotspot codon on tumor sequencing, which is highly specific for DICER1-related tumor predisposition (PP4, PMIDs: 27459524, 26033159).", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1703", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "This variant has been seen in 1 unrelated female without tumors through age 50 (BS2 not met; Ambry).\n", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1702/1704", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1703", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1702", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "contributionDate": { "date": "2026/3/23", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA129336/MONDO:0100216/024/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50050_EP165729564243098", "id": "CG-PCER-AGENT:CG_50050_EP165729564243098", "type": "Agent" }, "comments": "This variant received a total of 1 phenotype point across 2 unrelated probands meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMIDs: 3799599, 21205968; Internal Contributors).\nNote: all had thyroid phenotypes", "contributionDate": { "date": "2026/3/23", "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": "CA129336/MONDO:0100216/024/ci/CA129336/MONDO:0100216/024.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024/0/1606", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA129336/MONDO:0100216/024", "metadata": { "created": "2026-03-24T20:17:21.413Z", "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": "Tue, 24 Mar 2026 20:17:21 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "efaf6fc3-d5c9-4c9e-90d0-aa736abfd98d", "variant": { "@id": "https://reg.genome.network/allele/CA129336", "id": "CAR:CA129336", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_177438.3:c.2516C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_177438.3(DICER1):c.2516C>T (p.Ser839Phe)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T02:56:17.573Z" } }, "status": { "code": 200, "name": "OK" } }