{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/3caeeba8-927f-4038-995e-ba520590df07/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1577628936", "label": "ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH2 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0005835", "id": "MONDO:0005835", "label": "Lynch syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "It is not predicted to affect protein function (Prior_utah (MAPP/PP2) = 0.000107375002699 which is < than 0.11). Moreover, it is not predicted to affect splicing (max value SpliceAI 0 and Prior_utah_splicing_de_novo = 0.02).", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "Allelic frequency in gnomAD all non-cancer v2.1.1 = 0.09336%; MCAF 95% = 0.00934%.", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "Allelic frequency in gnomAD all non-cancer v2.1.1 = 0.09336%; MCAF 95% = 0.00934%. Allelic frequency in Bridges consortium: 11/53461 controls = 0.02% (PMID 33471991).", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1589", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "No effect on splicing (pCAS minigene [Pascaline Gaildrat & Stephanie Baert-Desurmont]). Proficient function in 1 calibrated assay (loss of function score -1,96 in Jia 2021; PMID 33357406; BS3)\n", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1579", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1580", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1579/1581", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "1 patient with CRC showing MSS/IHC normal (FHCRC CCFR, Insight database)", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1579", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "Allelic frequency in gnomAD all non-cancer v2.1.1 = 0.09336% and gnomAD v4.1 Grpmax AF = 0.007999%\t", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA019161/MONDO:0005835/137/ei/1/1703", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "contributionDate": { "date": "2024/10/11", "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/CA019161/MONDO:0005835/137/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841", "id": "CG-PCER-AGENT:CG_50099_EP167879163953841", "type": "Agent" }, "comments": "Co-observation with pathogenic variants in MLH1: MLH1 c.1852_1854del p.(Lys618del) (CRC age <50 Marseille UMD db entry); MLH1 c.589-1G>T (CRC age 35 Wagner et al., 2003, Chao et al., 2008). ", "contributionDate": { "date": "2024/10/11", "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": "CA019161/MONDO:0005835/137/ci/CA019161/MONDO:0005835/137.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1702/1704", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/1/1703", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137/0/1702", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA019161/MONDO:0005835/137", "metadata": { "created": "2024-10-11T02:47:17.164Z", "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": "Fri, 11 Oct 2024 02:47:17 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26334-5", "id": "LN:LA26334-5", "label": "Likely Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "3caeeba8-927f-4038-995e-ba520590df07", "variant": { "@id": "https://reg.genome.network/allele/CA019161", "id": "CAR:CA019161", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000251.3:c.1748A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000251.3(MSH2):c.1748A>G (p.Asn583Ser)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-09T14:16:00.161Z" } }, "status": { "code": 200, "name": "OK" } }