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      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1535438831",
      "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA2 Version 1.2",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.2"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0700269",
      "id": "MONDO:0700269",
      "label": "BRCA2-related cancer predisposition",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1828",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/ei/1/1829",
            "contribution": [
              {
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                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844",
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                },
                "contributionDate": {
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                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
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                },
                "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": [
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                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1828/1830",
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                        "comments": "Missense variant shown to alter splicing, functional data considered only from assays that measure effect via mRNA and protein. Reported by three calibrated studies incorporating mRNA splicing effects to exhibit function similar to pathogenic control variants (PMID:39779857, 39779848, 33293522) (PS3 met).",
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                        "type": "Contribution"
                      }
                    ],
                    "id": "CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
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                ],
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            ],
            "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/1/1829",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1828",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/ei/1/1595",
            "contribution": [
              {
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                  "type": "Agent"
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                "contributionDate": {
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                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
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                  "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/CA025666/MONDO:0700269/097/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844",
                          "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                          "type": "Agent"
                        },
                        "comments": "This variant is reported to result in aberrant mRNA splicing. RT-PCR demonstrated that the variant impacts splicing by skipping of exon 19 (PMIDs: 22505045, 16489001, 32123317) which results in the production of an in-frame transcript (r.8332_8487del p.(Ile2778_Gln2829del), PMID: 32123317). The effect is complete and no full length transcript is produced by the variant allele (PMID: 22505045, Internal lab collaborator). Appropriate code strength determined by comparison of results to PVS1 decision tree and assessment of mRNA splicing data (In-frame deletion variant of exon 19 that overlaps a (potentially) clinically important functional domain (DNA-binding domain) (PVS1 (RNA) met).",
                        "contributionDate": {
                          "date": "2026/9/21",
                          "description": "Date on which this evidence was provided"
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                        "contributionRole": {
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                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1594",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1831",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/ei/1/1832",
            "contribution": [
              {
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                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844",
                  "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                  "type": "Agent"
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                "contributionDate": {
                  "date": "2026/9/21",
                  "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/0018",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "0018",
              "label": "PP4",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1831/1833",
                "evidenceItem": [
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                          "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
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                        "comments": "Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 15.5 (based on Cosegregation LR=14.3; Pathology LR=1.90; PMID: 31131967 and Family History LR=0.569; PMID: 31853058), within the thresholds for moderate evidence towards pathogenicity (LR ≥4.3 & <18.7) (PP4_Moderate met).",
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                        "type": "Contribution"
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                    ],
                    "id": "CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1831/1833",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/1/1832",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1831",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/ei/1/1748",
            "contribution": [
              {
                "agent": {
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                  "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/21",
                  "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/CA025666/MONDO:0700269/097/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
                    "contribution": [
                      {
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                          "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                          "type": "Agent"
                        },
                        "comments": "This BRCA2 missense variant has a SpliceAI score of 0.36, predicting an impact on splicing (score threshold ≥0.2) (PP3 not applied because a PVS1 code is met).\n",
                        "contributionDate": {
                          "date": "2026/9/21",
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                          "label": "curator role",
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                        "type": "Contribution"
                      }
                    ],
                    "id": "CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025666/MONDO:0700269/097/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844",
                  "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/21",
                  "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/CA025666/MONDO:0700269/097/el/0/1636/1638",
                "evidenceItem": [
                  {
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                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                          "type": "Agent"
                        },
                        "comments": "This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met).",
                        "contributionDate": {
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                          "id": "SEPIO:0000516",
                          "label": "curator role",
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                      }
                    ],
                    "id": "CA025666/MONDO:0700269/097/ci/CA025666/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097/0/1636",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA025666/MONDO:0700269/097",
    "metadata": {
      "created": "2026-10-15T19:00:43.132Z",
      "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": "Thu, 15 Oct 2026 19:00:43 -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": "898d1843-e31f-4d56-b9be-0a164e5cdd9e",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA025666",
      "id": "CAR:CA025666",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000059.4:c.8486A>G"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000059.4(BRCA2):c.8486A>G (p.Gln2829Arg)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-26T00:07:45.915Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}