{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/89d53e74-33f3-465b-abde-d4f656802fed/doc/sepio/version/2.1.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243118", "label": "ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MAP2K2 Version 2.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021060", "id": "MONDO:0021060", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/10/2", "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/CA137966/MONDO:0021060/048/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The filtering allele frequency in gnomAD v4.1.0 is 0.01543%\t (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).", "contributionDate": { "date": "2024/10/2", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/10/2", "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/CA137966/MONDO:0021060/048/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The filtering allele frequency in gnomAD v4.1.0 is 0.01543%\t (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).", "contributionDate": { "date": "2024/10/2", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/10/2", "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/CA137966/MONDO:0021060/048/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "REVEL gives a score of 0.219, which predicts no impact on protein function (BP4). ", "contributionDate": { "date": "2024/10/2", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/10/2", "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/CA137966/MONDO:0021060/048/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The filtering allele frequency in gnomAD v4.1.0 is 0.01543%\t (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).", "contributionDate": { "date": "2024/10/2", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/10/2", "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/CA137966/MONDO:0021060/048/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "REVEL gives a score of 0.219, which predicts no impact on protein function (BP4). ", "contributionDate": { "date": "2024/10/2", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/10/2", "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/CA137966/MONDO:0021060/048/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Identified in 4 independent occurrences in patients with disparate phenotypes (PS4 not met; GeneDx, Laboratory for Molecular Medicine internal data; ClinVar SCV000207950.9; SCV000063182.5).", "contributionDate": { "date": "2024/10/2", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048", "metadata": { "created": "2024-10-02T20:16:58.152Z", "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": "Wed, 02 Oct 2024 20:16:58 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "89d53e74-33f3-465b-abde-d4f656802fed", "variant": { "@id": "https://reg.genome.network/allele/CA137966", "id": "CAR:CA137966", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.4:c.784G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.4(MAP2K2):c.784G>A (p.Val262Ile)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/89d53e74-33f3-465b-abde-d4f656802fed/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243118", "label": "ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MAP2K2 Version 2.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021060", "id": "MONDO:0021060", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/9/27", "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/0070", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0070", "label": "BS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The filtering allele frequency in gnomAD v4.1.0 is 0.01543%\t (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).", "contributionDate": { "date": "2024/9/27", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/9/27", "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/0011", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0011", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The filtering allele frequency in gnomAD v4.1.0 is 0.01543%\t (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).", "contributionDate": { "date": "2024/9/27", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/9/27", "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/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "REVEL gives a score of 0.219, which predicts no impact on protein function (BP4). ", "contributionDate": { "date": "2024/9/27", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/9/27", "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/0080", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0080", "label": "BP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "REVEL gives a score of 0.219, which predicts no impact on protein function (BP4). ", "contributionDate": { "date": "2024/9/27", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/9/27", "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/0087", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000325", "id": "SEPIO:0000325", "label": "Benign Stand Alone" }, "id": "0087", "label": "BA1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The filtering allele frequency in gnomAD v4.1.0 is 0.01543%\t (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).", "contributionDate": { "date": "2024/9/27", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2024/9/27", "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/0053", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0053", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/048/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Identified in 4 independent occurrences in patients with disparate phenotypes (PS4 not met; GeneDx, Laboratory for Molecular Medicine internal data; ClinVar SCV000207950.9; SCV000063182.5).", "contributionDate": { "date": "2024/9/27", "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": "CA137966/MONDO:0021060/048/ci/CA137966/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/048", "metadata": { "created": "2024-09-28T06:07:44.631Z", "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 06:07:44 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "89d53e74-33f3-465b-abde-d4f656802fed", "variant": { "@id": "https://reg.genome.network/allele/CA137966", "id": "CAR:CA137966", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.4:c.784G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.4(MAP2K2):c.784G>A (p.Val262Ile)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/89d53e74-33f3-465b-abde-d4f656802fed/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021060", "id": "MONDO:0021060", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/0080", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0080", "label": "BP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/004/ci/CA137966/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Computational prediction tools and conservation analysis suggest that the p.Val262Ile variant does not impact the protein (BP4).", "contributionDate": { "date": "2020/7/1", "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": "CA137966/MONDO:0021060/004/ci/CA137966/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/0053", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0053", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/004/ci/CA137966/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Identified in 4 independent occurrences in patients with disparate phenotypes (PS4 not met; GeneDx, Laboratory for Molecular Medicine internal data; ClinVar SCV000207950.9; SCV000063182.5).", "contributionDate": { "date": "2020/7/1", "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": "CA137966/MONDO:0021060/004/ci/CA137966/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/0070", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0070", "label": "BS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA137966/MONDO:0021060/004/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA137966/MONDO:0021060/004/ci/CA137966/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "This variant was present in 0.029% (95% CI of 8/13654) of Latino alleles in gnomAD (BS1).", "contributionDate": { "date": "2020/7/1", "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": "CA137966/MONDO:0021060/004/ci/CA137966/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004/0/1804", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA137966/MONDO:0021060/004", "metadata": { "created": "2024-09-27T21:06:57.195Z", "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, 27 Sep 2024 21:06:57 -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": "89d53e74-33f3-465b-abde-d4f656802fed", "variant": { "@id": "https://reg.genome.network/allele/CA137966", "id": "CAR:CA137966", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.3:c.784G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.3(MAP2K2):c.784G>A (p.Val262Ile)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T23:54:53.898Z" } }, "status": { "code": 200, "name": "OK" } }