{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/712094bd-7187-4f2b-bc0f-90c0275d5d2f/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637583", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1", "type": "VariantPathogenicityInterpretationGuideline", "url": "https://clinicalgenome.org/docs/clingen-platelet-disorders-expert-panel-specifications-to-the-acmg-amp-variant-interpretation-guidelines-version-2.1/", "version": "2.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100326", "id": "MONDO:0100326", "label": "Glanzmann thrombasthenia", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1630", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/ei/1/1631", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2024/8/20", "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/0040", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0040", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1630/1632", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "This variant was observed in homozygosity in a proband (GT-15 in PMID: 30792900) and two affected family members (also in homozygosity; FAM-03 GT-16 and GT-17 in PMID: 30792900).", "contributionDate": { "date": "2024/8/20", "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": "CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1630/1632", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/1/1631", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1630", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2024/8/20", "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/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "This variant has been observed in homozygosity in at least two probands (GT-11 and GT-15 in PMID: 30792900). Each occurrence earns 0.5 points, which is sufficient to apply PM3.", "contributionDate": { "date": "2024/8/20", "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": "CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2024/8/20", "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/CA400023600/MONDO:0100326/011/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "A different missense change at this amino acid residue (c.728A>T, p.Asp243Val) has been reported in a Glanzmann thrombasthenia patient (PMID: 18832906). However this evidence was not counted toward the interpretation of the c.727G>C variant to avoid circularity.", "contributionDate": { "date": "2024/8/20", "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": "CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2024/8/20", "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://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4.0 is 0.000002856 (1/350098 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).", "contributionDate": { "date": "2024/8/20", "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": "CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2024/8/20", "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/CA400023600/MONDO:0100326/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "REVEL score of 0.983 is above the >.0.7 threshold to support a deleterious effect.", "contributionDate": { "date": "2024/8/20", "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": "CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2024/8/20", "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/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400023600/MONDO:0100326/011/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "This variant has been observed in at least two probands with a previous history of Glanzmann's thrombasthenia (GT-11 and GT-15 in PMID: 30792900), but sufficient platelet aggregation and surface protein expression information was not provided to apply PP4 at any strength level.", "contributionDate": { "date": "2024/8/20", "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": "CA400023600/MONDO:0100326/011/ci/CA400023600/MONDO:0100326/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011/0/1633", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400023600/MONDO:0100326/011", "metadata": { "created": "2024-09-28T05:32:55.177Z", "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 05:32:55 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "712094bd-7187-4f2b-bc0f-90c0275d5d2f", "variant": { "@id": "https://reg.genome.network/allele/CA400023600", "id": "CAR:CA400023600", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000212.3:c.727G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000212.3(ITGB3):c.727G>C (p.Asp243His)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T15:01:31.877Z" } }, "status": { "code": 200, "name": "OK" } }