{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/81ad1388-e2c1-4808-a45b-a3a6439d1026/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010119", "id": "MONDO:0010119", "label": "Glanzmann's thrombasthenia", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/28", "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/0060", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0060", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/EV000001230", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Two affected siblings, both homozygous, were reported as Patients LW and GW.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/EV000001230", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/10607701", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/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": "2021/1/28", "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/CA399805793/MONDO:0010119/011/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/CA399805793/MONDO:0010119/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "SIFT, PolyPhen, and MutationTaster agree that there is a deleterious effect caused by this variant; the revel score of 0.825 is greater than the >0.7 threshold.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/CA399805793/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/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": "2021/1/28", "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/CA399805793/MONDO:0010119/011/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/CA399805793/MONDO:0010119/011.002", "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 is absent from all population cohorts in gnomAD, ExAC, 1000 Genomes, and ESP.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/CA399805793/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/ei/1/1739", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/28", "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/005", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "005", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/EV000001230", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The proband, Patient LW, meets all the GT criteria for PP4. There is a history of mucocutaneous bleeding, including epistaxis, purpura, and petechiae. The patient has a normal platelet count and the expected aggregation results; platelets fail to aggregate to thrombin, ADP, epinephrine, or collagen but agglutinate normally in the presence of ristocetin. Surface expression was reduced as measured by flow cytometry; with monoclonal antibodies specific for αIIb, β3, and αIIbβ3 revealed that they respectively bound ∼10%, ∼20%, and ∼30%. Additionally platelets were unable to bind PAC-1 following platelet stimulation by phorbol myristate acetate.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/EV000001230", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/10607701", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/EV000001239", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Patient MR has mucocutaneous bleeding including epistaxis (reported in the GT database), platelet aggregation was absent in response to ADP and epinephrine but normal for ristocetin. Surface expression was <10% as measured by flow cytometry. A normal platelet count was not reported.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/EV000001239", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12083483", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/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": "2021/1/28", "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/CA399805793/MONDO:0010119/011/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/CA399805793/MONDO:0010119/011.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Two additional variants likely pathogenic variants 176Leu and 176His occur at the same amino acid residue as Pro176Ala, not included here to avoid circularity.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/CA399805793/MONDO:0010119/011.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/28", "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/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/EV000001230", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Pro176Ala (reported here as Pro145Ala) was expressed in COS-1 cells with WT β3 and resulted in complexes without the heavy chain such that little αIIbβ3 was detectable on the surface of these cells by immunoprecipitation (neither flow cytometry or Western blotting was used to measure expression). Additionally, they stably expressed αIIbP145Aβ3 and wild-type αIIbβ3 in CHO cells and found 2.5-fold less spontaneous adhesion of immobilized fibrinogen, compared to WT, and little increase in adhesion following exposure to PT25-2 (which normally doubles adherence). For soluble fibrinogen; whereas there was substantial PT25-2–stimulated fibrinogen binding to cells expressing wild-type αIIbβ3, there was none to cells expressing αIIbP145Aβ3.\n\nThese experiments indicate that not only does mutation of αIIbP145A attenuate the ability of αIIbβ3 to interact with immobilized fibrinogen, but it abolishes the ability of αIIbβ3 to bind soluble fibrinogen.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/EV000001230", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/10607701", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/28", "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/0027", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0027", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA399805793/MONDO:0010119/011/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/EV000001230", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/EV000001230", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/10607701", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA399805793/MONDO:0010119/011/ci/EV000001239", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Patient MR is compound heterozygous for the Ile405Thr (reported as Ile374Thr) variant and Pro176Ala (reported as Pro145Ala). The variants were reported to have been confirmed to be in the trans phase. This variant is used as evidence to support PM3 for Ile405Thr, as such it is not used here to avoid a circular argument.", "contributionDate": { "date": "2021/1/28", "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": "CA399805793/MONDO:0010119/011/ci/EV000001239", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12083483", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA399805793/MONDO:0010119/011", "metadata": { "created": "2024-09-27T21:31:31.876Z", "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 21:31:31 -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": "81ad1388-e2c1-4808-a45b-a3a6439d1026", "variant": { "@id": "https://reg.genome.network/allele/CA399805793", "id": "CAR:CA399805793", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000419.4:c.526C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000419.4:c.526C>G" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T04:57:40.401Z" } }, "status": { "code": 200, "name": "OK" } }