{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/dfec0bf2-cccf-4932-8cf2-6dabf182615f/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/CA403385475/MONDO:0021060/004/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/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": "2020/3/23", "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" } ], "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/CA403385475/MONDO:0021060/004/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA403385475/MONDO:0021060/004/ci/CA403385475/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": "Present in 0.007324% (1/13654) of Latino chromosomes in gnomAD v3. Absent from gnomAD v2.1.1.", "contributionDate": { "date": "2020/3/23", "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": "CA403385475/MONDO:0021060/004/ci/CA403385475/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/el/0/1837", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/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": "2020/3/23", "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" } ], "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/CA403385475/MONDO:0021060/004/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA403385475/MONDO:0021060/004/ci/CA403385475/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": "MAP2K2 is a missense-constrained gene.", "contributionDate": { "date": "2020/3/23", "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": "CA403385475/MONDO:0021060/004/ci/CA403385475/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1837", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/ei/1/1703", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/3/23", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0069", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0069", "label": "BS2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA403385475/MONDO:0021060/004/ci/CA403385475/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 seen in 3 unaffected individuals (Invitae internal data, SCV000817942.1; Baylor internal data). One case was a juvenile male tested because his father had idiopathic HCM, but the proband was supposedly unaffected and healthy. This case was not counted because the indication for testing was HCM. In 2 other cases, the variant was inherited and the fathers of the probands were noted to be asymptomatic. One proband was suspected to have NS; the other did not have a diagnosis.", "contributionDate": { "date": "2020/3/23", "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": "CA403385475/MONDO:0021060/004/ci/CA403385475/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1702/1704", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/1/1703", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1702", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/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": "2020/3/23", "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" } ], "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/CA403385475/MONDO:0021060/004/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA403385475/MONDO:0021060/004/ci/CA403385475/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": "Does not occur between aa 47-65 or 128-138.", "contributionDate": { "date": "2020/3/23", "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": "CA403385475/MONDO:0021060/004/ci/CA403385475/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/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": "2020/3/23", "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" } ], "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/CA403385475/MONDO:0021060/004/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA403385475/MONDO:0021060/004/ci/CA403385475/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": "Only 1 other variant in this codon, c.841C>T (p.Arg281Trp), has been reported. It was absent from ClinVar and was classified as a VUS by the EP.", "contributionDate": { "date": "2020/3/23", "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": "CA403385475/MONDO:0021060/004/ci/CA403385475/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/MONDO:0021060/004/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA403385475/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": "2020/3/23", "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" } ], "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/CA403385475/MONDO:0021060/004/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA403385475/MONDO:0021060/004/ci/CA403385475/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": "REVEL score 0.032. May add a 3' splice site (predicted by SpliceSiteFinder-like and MaxEntScan but not NNSPLICE or GeneSplicer), however impact to splicing is not predicted to align with the GOF mechanism for MAP2K2-associated RASopathy. 1 animal in the UCSC database (guinea pig) has Q at this site.", "contributionDate": { "date": "2020/3/23", "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": "CA403385475/MONDO:0021060/004/ci/CA403385475/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004/0/1684", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA403385475/MONDO:0021060/004", "metadata": { "created": "2024-09-27T20:36:16.024Z", "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 20:36:15 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "dfec0bf2-cccf-4932-8cf2-6dabf182615f", "variant": { "@id": "https://reg.genome.network/allele/CA403385475", "id": "CAR:CA403385475", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_030662.3:c.842G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_030662.3(MAP2K2):c.842G>A (p.Arg281Gln)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T03:15:16.227Z" } }, "status": { "code": 200, "name": "OK" } }