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"label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/048/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "This variant was reported in 1 proband with a RASopathy (PS4_Supporting, PMID: 2035858)", "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": "CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1606", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048", "metadata": { "created": "2024-10-02T20:16:51.426Z", "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 20:16:51 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "3.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "307f4b6c-ef49-48bd-98e2-5cf382642800", "variant": { "@id": "https://reg.genome.network/allele/CA279962", "id": "CAR:CA279962", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.4:c.383C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/307f4b6c-ef49-48bd-98e2-5cf382642800/doc/sepio/version/3.0.0", "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:0015280", "id": "MONDO:0015280", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/048/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/048/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/CA279962/MONDO:0015280/048/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Computational prediction tools and conservation analysis suggest that the p.Pro124Gln variant may impact the protein (PP3).", "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": "CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/048/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/048/ei/1/1637", "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": 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"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/CA279962/MONDO:0015280/048/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Not applied as there were not enough probands with the other variants. 2 other missense change observed in the residue, 1 pathogenic missense variant (p.Pro128Leu; ClinVar: 666272) and \n1 VUS missense variant (p.Pro128Arg; ClinVar: 40792)", "contributionDate": { "date": "2024/10/2", "description": 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family members (PP1_S; PMID: 20358587).", "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": "CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/048/el/0/1804", "evidenceItem": [ { "@id": 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vitro functional studies showed that the p.Pro124Gln variant increased ERK phosphorylation compared to wild-type (PS3; PMID 20358587).", "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": "CA279962/MONDO:0015280/048/ci/CA279962/MONDO:0015280/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048/0/1696", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/048", "metadata": { "created": "2024-10-02T13:10:15.023Z", "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 13:10:14 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "3.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "307f4b6c-ef49-48bd-98e2-5cf382642800", "variant": { "@id": "https://reg.genome.network/allele/CA279962", "id": "CAR:CA279962", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.4:c.383C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/307f4b6c-ef49-48bd-98e2-5cf382642800/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/CA279962/MONDO:0021060/048/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/ei/1/1697", "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/0045", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0045", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0021060/048/ci/CA279962/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": "In vitro functional studies showed that the p.Pro124Gln variant increased ERK phosphorylation compared to wild-type (PS3; PMID 20358587).", "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": "CA279962/MONDO:0021060/048/ci/CA279962/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/ei/1/1616", "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/006", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "006", "label": "PM1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0021060/048/ci/CA279962/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 variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a critical functional domain of MAP2K2 ( AA 128-138, PM1).", "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": "CA279962/MONDO:0021060/048/ci/CA279962/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/ei/1/1781", "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/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/CA279962/MONDO:0021060/048/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0021060/048/ci/CA279962/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": "Not applied as there were not enough probands with the other variants. 2 other missense change observed in the residue, 1 pathogenic missense variant (p.Pro128Leu; ClinVar: 666272) and \n1 VUS missense variant (p.Pro128Arg; ClinVar: 40792)", "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": "CA279962/MONDO:0021060/048/ci/CA279962/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1837", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/ei/1/1838", "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/0061", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0061", "label": "PP2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0021060/048/ci/CA279962/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" }, "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": "CA279962/MONDO:0021060/048/ci/CA279962/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1837", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/ei/1/1748", "contribution": [ { "agent": { "@id": 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"type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0021060/048/ci/CA279962/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": "This variant is absent from gnomAD v4.1.0", "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": "CA279962/MONDO:0021060/048/ci/CA279962/MONDO:0021060/048.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0021060/048/0/1636/1638", "type": "EvidenceLine" } ], "id": 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{ "@id": "https://obofoundry.org/sepio/clingen/0032", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0032", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0021060/048/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA279962/MONDO:0021060/048/ci/CA279962/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": "This variant was reported in 1 proband with a RASopathy (PS4_Supporting, PMID: 2035858)", "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": 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We expect it to differ significantly from the final schema.", "producedAtUTC": "Sat, 28 Sep 2024 06:07:52 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "307f4b6c-ef49-48bd-98e2-5cf382642800", "variant": { "@id": "https://reg.genome.network/allele/CA279962", "id": "CAR:CA279962", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.4:c.383C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/307f4b6c-ef49-48bd-98e2-5cf382642800/doc/sepio/version/1.0.0", "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:0015280", "id": "MONDO:0015280", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/004/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA279962/MONDO:0015280/004/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155189947580566", "id": "CG-PCER-AGENT:CG_50021_EP155189947580566", "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", 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"This variant is absent from gnomAD v4.1.0", "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": "CA279962/MONDO:0015280/004/ci/CA279962/MONDO:0015280/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/004/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/004/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/004/0/1804", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA279962/MONDO:0015280/004", "metadata": { "created": "2024-09-27T19:46:29.201Z", "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 19:46:29 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "307f4b6c-ef49-48bd-98e2-5cf382642800", "variant": { "@id": "https://reg.genome.network/allele/CA279962", "id": "CAR:CA279962", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.4:c.383C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T19:01:21.368Z" } }, "status": { "code": 200, "name": "OK" } }