{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/fc109f7d-50fd-4565-b5f2-92828c117ff9/doc/sepio/version/1.0.0",
    "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/CA400034189/MONDO:0100326/011/el/0/1696",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/ei/1/1697",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392",
                  "id": "CG-PCER-AGENT:CG_50040_EP161161244771392",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/5/3",
                  "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/CA400034189/MONDO:0100326/011/el/0/1696/1698",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA400034189/MONDO:0100326/011/ci/CA400034189/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": "Surface expression of αIIb and β3 measured by Western blot in HEK293T cells transiently co-transfected with the c.2222G>A (p.Trp741Ter) variant β3 and wild type αIIb and β3 showed decreased\nexpression at 0% WT levels, indicating that this variant impacts protein function (PMID: 37604334) (PS3). Downgraded for a nonsense variant meeting PVS1.\n\n",
                        "contributionDate": {
                          "date": "2024/5/3",
                          "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": "CA400034189/MONDO:0100326/011/ci/CA400034189/MONDO:0100326/011.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1696/1698",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/1/1697",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1696",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/ei/1/1595",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392",
                  "id": "CG-PCER-AGENT:CG_50040_EP161161244771392",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/5/3",
                  "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/0017",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000220",
                "id": "SEPIO:0000220",
                "label": "Pathogenic Very Strong"
              },
              "id": "0017",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA400034189/MONDO:0100326/011/ci/CA400034189/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 c.2222G>A (p.Trp741Ter) variant in exon 14 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 14 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). ",
                        "contributionDate": {
                          "date": "2024/5/3",
                          "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": "CA400034189/MONDO:0100326/011/ci/CA400034189/MONDO:0100326/011.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1594",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/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": "2024/5/3",
                  "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/CA400034189/MONDO:0100326/011/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA400034189/MONDO:0100326/011/ci/CA400034189/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": "At least one patient (Proband from PMID: 37604334) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to 0.25% as measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries. (PP4_strong). ",
                        "contributionDate": {
                          "date": "2024/5/3",
                          "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": "CA400034189/MONDO:0100326/011/ci/CA400034189/MONDO:0100326/011.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/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": "2024/5/3",
                  "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/CA400034189/MONDO:0100326/011/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA400034189/MONDO:0100326/011/ci/CA400034189/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 detected in at least 1 proband with Glanzmann thrombasthenia (PMID: 37604334). This individual was compound heterozygous for this variant and a plausibly pathogenic SINE-VNTR-Alu (SVA) retrotransposon insertion in ITGB3. The variants were confirmed in trans by parental testing. \n\nThe insertion has not been curated by the PD-VCEP (PM3_NotMet). SVA element was inserted in a sense orientation in intron 11 of ITGB3, resulting in aberrant splicing of ITGB3.",
                        "contributionDate": {
                          "date": "2024/5/3",
                          "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": "CA400034189/MONDO:0100326/011/ci/CA400034189/MONDO:0100326/011.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1717",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/MONDO:0100326/011/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400034189/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": "2024/5/3",
                  "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/CA400034189/MONDO:0100326/011/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA400034189/MONDO:0100326/011/ci/CA400034189/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 is absent from gnomAD v4.0.0 (PM2_Supporting).",
                        "contributionDate": {
                          "date": "2024/5/3",
                          "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": "CA400034189/MONDO:0100326/011/ci/CA400034189/MONDO:0100326/011.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011/0/1636",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA400034189/MONDO:0100326/011",
    "metadata": {
      "created": "2024-09-28T04:35:59.389Z",
      "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 04:35:59 -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": "fc109f7d-50fd-4565-b5f2-92828c117ff9",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA400034189",
      "id": "CAR:CA400034189",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000212.3:c.2222G>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000212.3:c.2222G>A"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-05T21:51:41.203Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}