{
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    "@id": "https://cgerepoapi/evrepo/api/summary/classification/393b5f9f-c4b7-4db7-a443-11d099ae1c2a/doc/sepio/version/1.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1529292791",
      "label": "ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "2.1.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021056",
      "id": "MONDO:0021056",
      "label": "familial adenomatous polyposis 1",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/el/0/1762",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/ei/1/1763",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841",
                  "id": "CG-PCER-AGENT:CG_50099_EP167879163953841",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/5/19",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/el/0/1762/1764",
                "evidenceItem": [
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                    "@id": "CG-PCER:curatorInference/CA16022245/MONDO:0021056/089/ci/CA16022245/MONDO:0021056/089.002",
                    "contribution": [
                      {
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                          "id": "CG-PCER-AGENT:CG_50099_EP167879163953841",
                          "type": "Agent"
                        },
                        "comments": "The NM_000038.6(APC):c.422G>A (p.Arg141Lys) variant in APC is a G to non-G change at the last nucleotide of exon 4. It is predicted to cause skipping of exon 4, resulting in a frameshift in a gene in which loss-of-function is an established disease mechanism (List B; PVS1_Strong). However, exon skipping could not be confirmed by RTPCRSeq data. Even though this could be based on technical limitations, the variant allele was present in 35% of normally spliced reads, so the splicing impact seems to be low (internal data Ambry Genetics). ",
                        "contributionDate": {
                          "date": "2025/5/19",
                          "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": "CA16022245/MONDO:0021056/089/ci/CA16022245/MONDO:0021056/089.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/0/1762/1764",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/1/1763",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/0/1762",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/el/0/1702",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/ei/1/1703",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841",
                  "id": "CG-PCER-AGENT:CG_50099_EP167879163953841",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/5/19",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/el/0/1702/1704",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA16022245/MONDO:0021056/089/ci/CA16022245/MONDO:0021056/089.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841",
                          "id": "CG-PCER-AGENT:CG_50099_EP167879163953841",
                          "type": "Agent"
                        },
                        "comments": "The variant has been reported in three individuals without a colorectal cancer/polyposis associated phenotype (one person fulfills 0.5 points as a “healthy individual,” for the other two not enough information is available; BS2 not met; internal data Ambry Genetics). ",
                        "contributionDate": {
                          "date": "2025/5/19",
                          "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": "CA16022245/MONDO:0021056/089/ci/CA16022245/MONDO:0021056/089.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/0/1702/1704",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/1/1703",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/0/1702",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841",
                  "id": "CG-PCER-AGENT:CG_50099_EP167879163953841",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/5/19",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16022245/MONDO:0021056/089/el/0/1636/1638",
                "evidenceItem": [
                  {
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                    "contribution": [
                      {
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                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50099_EP167879163953841",
                          "id": "CG-PCER-AGENT:CG_50099_EP167879163953841",
                          "type": "Agent"
                        },
                        "comments": "The total minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.0004% (1/236810 alleles), which is lower than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) threshold of < 0.001% (0.00001) for PM2_Supporting if the allele count is ≤ 1 and therefore meets this criterion (PM2_Supporting). ",
                        "contributionDate": {
                          "date": "2025/5/19",
                          "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": "CA16022245/MONDO:0021056/089/ci/CA16022245/MONDO:0021056/089.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089/0/1636",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA16022245/MONDO:0021056/089",
    "metadata": {
      "created": "2025-05-19T18:24:11.866Z",
      "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": "Mon, 19 May 2025 18:24:11 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "1.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA26333-7",
      "id": "LN:LA26333-7",
      "label": "Uncertain Significance"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "393b5f9f-c4b7-4db7-a443-11d099ae1c2a",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA16022245",
      "id": "CAR:CA16022245",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000038.6:c.422G>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000038.6(APC):c.422G>A (p.Arg141Lys)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-14T12:59:36.008Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}