{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/919a92fa-b50b-4d78-ad70-26b081a7dc4d/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637581", "label": "ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0018875", "id": "MONDO:0018875", "label": "Li-Fraumeni syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1636", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/ei/1/1637", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "comments": "This variant has an allele frequency of 0.0000111525 (18/1613988 alleles) across gnomAD v4.1.0 (after removing low AB alleles likely to represent CHIP contamination and recalculating total allele frequency) which is lower than the Clingen TP53 VCEP threshold (<0.00003) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).", "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1636", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1684", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/ei/1/1685", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "comments": "BP4_MODERATE APPLIED\n\nComputational predictor scores (BayesDel = -0.232; Align GVGD Class C0) are below the recommended thresholds (BayesDel ≤ -0.008 and an Align GVGD Class ≤ 55), evidence that does not predict a damaging effect on TP53 via protein change. SpliceAI predicts that the variant has no impact on splicing (BP4_Moderate).", "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1684", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1777", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/ei/1/1778", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": 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"evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": 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"id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0051", "label": "PS2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1663/1665", "type": "EvidenceLine" } ], "id": 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"https://obofoundry.org/sepio/clingen/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1828", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1615", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/ei/1/1616", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50013_EP157160812228644", "id": "CG-PCER-AGENT:CG_50013_EP157160812228644", "type": "Agent" }, "comments": "This variant does not reside within a region of TP53 that is defined as a mutational hotspot by the ClinGen TP53 VCEP (PM1 not met).", "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1615", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/el/0/1780", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA000056/MONDO:0018875/009/ei/1/1781", "contribution": [ { "agent": { "@id": 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However, these variants have not yet met the criteria to be classified as pathogenic or likely pathogenic by the ClinGen TP53 VCEP’s specifications (PM5 not met).", "contributionDate": { "date": "2024/8/5", "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": "CA000056/MONDO:0018875/009/ci/CA000056/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000056/MONDO:0018875/009/0/1780", "type": "EvidenceLine" }, { "@id": 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We expect it to differ significantly from the final schema.", "producedAtUTC": "Mon, 23 Sep 2024 22:45:19 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6675-8", "id": "LN:LA6675-8", "label": "Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "919a92fa-b50b-4d78-ad70-26b081a7dc4d", "variant": { "@id": "https://reg.genome.network/allele/CA000056", "id": "CAR:CA000056", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000546.5:c.145G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000546.5(TP53):c.145G>A (p.Asp49Asn)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-06-07T06:33:56.390Z" } }, "status": { "code": 200, "name": "OK" } }