DEL chr7:72,846,244-74,187,855

CNV summary

Our verdict is Pathogenic. Variant got ACMG score 1.45.

CNV loss of the region 7:72,846,244-74,187,855 (1.3 mb), is localized in (7)(q11.23). The region contains protein-coding and important regions. There is complete overlap with established HI region(s): dbVar:nssv15137072, dbVar:nssv15167740 (and 21 more). Among those, regions with breakpoints not laying inside the transcripts: morbid:DNAJC30, morbid:ELN (and 2 more). There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50 (and 16 more) in the affected region.

Genes

TODO

ClinGen

TODO
Variant links:

ACMG Results

Pathogenicity Level: Pathogenic

Score: 1.45

Criteria:

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Debug

show
{
  "cnvChange": {
    "chr": "7",
    "start": 72846244,
    "end": 74187855,
    "svType": "DEL"
  },
  "annotations": {
    "chr": "7",
    "start": 72846244,
    "end": 74187855,
    "svType": "DEL",
    "length": 1341611,
    "geneGroups": [
      "Nucleoporins",
      "Tripartite motif family|Ring finger proteins",
      "Speedy/RINGO cell cycle regulator family",
      "NOP2/Sun RNA methyltransferase family",
      "FKBP prolyl isomerases",
      "CD molecules|G protein-coupled receptors, Class F frizzled",
      "PHD finger proteins|Bromodomain containing|B-WICH chromatin-remodelling complex subunits",
      "BAF complex",
      "WD repeat domain containing",
      "Basic helix-loop-helix proteins",
      "ESCRT-I",
      "DNAJ (HSP40) heat shock proteins",
      "Ribosomal biogenesis factors|7BS DNA/RNA methyltransferases",
      "Syntaxins",
      "Abhydrolase domain containing",
      "Claudins",
      "7BS orphan methyltransferases",
      "LIM domain containing|PDZ domain containing|LIMK/TESK kinase family",
      "RNA binding motif containing|MicroRNA protein coding host genes"
    ],
    "cytobandString": "(7)(q11.23)",
    "overlappedGenes": [
      {
        "id": "NM_022170.2",
        "chr": "7",
        "start": 74174356,
        "end": 74197096,
        "regionType": "GENE",
        "overlapType": "FIVE_UTR_WITH_CDS",
        "coveredFraction": 0.1072961373390558,
        "hgncId": 12741,
        "geneSummaryLongCarrier": {
          "symbol": "EIF4H",
          "proteinCoding": true,
          "maneSelectEnsemblId": "ENST00000265753.13",
          "maneSelectRefSeqId": "NM_022170.2",
          "lof_pLI": 0.97545,
          "lof_oe_ci_upper": 0.508,
          "decipherHi": 0.2178,
          "geneGroup": "RNA binding motif containing|MicroRNA protein coding host genes"
        },
        "overlappedGenePart": {
          "cdsBasesLost": 247,
          "cdsBasesSize": 747,
          "cdsFractionLost": 0.33065595716198126,
          "exonsBasesLost": 275,
          "exonsBasesSize": 2563,
          "exonsFractionLost": 0.1072961373390558,
          "lostExons": 2,
          "lostExonsRanks": [
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            1
          ],
          "readingFrameDestroyed": true,
          "overlapType": "FIVE_UTR_WITH_CDS",
          "numberOfPLpVariantsCovered": 0,
          "escapeNmd": false
        }
      },
      {
        "id": "NM_002314.4",
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        "start": 74083804,
        "end": 74122525,
        "regionType": "GENE",
        "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
        "coveredFraction": 1,
        "hgncId": 6613,
        "geneSummaryLongCarrier": {
          "symbol": "LIMK1",
          "proteinCoding": true,
          "maneSelectEnsemblId": "ENST00000336180.7",
          "maneSelectRefSeqId": "NM_002314.4",
          "lof_pLI": 1,
          "lof_oe_ci_upper": 0.338,
          "decipherHi": 0.1966,
          "clingenHi": "NO_EVIDENCE_AVAILABLE",
          "clingenTs": "NO_EVIDENCE_AVAILABLE",
          "geneGroup": "LIM domain containing|PDZ domain containing|LIMK/TESK kinase family"
        },
        "overlappedGenePart": {
          "cdsBasesLost": 1944,
          "cdsBasesSize": 1944,
          "cdsFractionLost": 1,
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          "exonsFractionLost": 1,
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          "lostExonsRanks": [
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          "readingFrameDestroyed": false,
          "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
          "numberOfPLpVariantsCovered": 0,
          "escapeNmd": false
        },
        "triploinsufficiencyType": "NO_EVIDENCE_AVAILABLE",
        "haploinsufficiencyType": "NO_EVIDENCE_AVAILABLE"
      },
      {
        "id": "NM_000501.4",
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        "regionType": "GENE",
        "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
        "coveredFraction": 1,
        "hgncId": 3327,
        "geneSummaryLongCarrier": {
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          "diseaseAssociations": [
            {
              "classification": "DEFINITIVE",
              "diseaseName": "supravalvular aortic stenosis",
              "diseaseId": "MONDO:0008504",
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              "source": "GENCC"
            },
            {
              "classification": "STRONG",
              "diseaseName": "cutis laxa, autosomal dominant 1",
              "diseaseId": "MONDO:0007411",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "STRONG",
              "diseaseName": "cutis laxa, autosomal dominant 1",
              "diseaseId": "MONDO:0007411",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "STRONG",
              "diseaseName": "cutis laxa, autosomal dominant 1",
              "diseaseId": "MONDO:0007411",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "DEFINITIVE",
              "diseaseName": "supravalvular aortic stenosis",
              "diseaseId": "MONDO:0008504",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "DEFINITIVE",
              "diseaseName": "cutis laxa, autosomal dominant 1",
              "diseaseId": "MONDO:0007411",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "SUPPORTIVE",
              "diseaseName": "supravalvular aortic stenosis",
              "diseaseId": "MONDO:0008504",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "SUPPORTIVE",
              "diseaseName": "autosomal dominant cutis laxa",
              "diseaseId": "MONDO:0019571",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "STRONG",
              "diseaseName": "cutis laxa, autosomal dominant 1",
              "diseaseId": "MONDO:0007411",
              "inheritanceMode": null,
              "source": "GENCC"
            },
            {
              "classification": "STRONG",
              "diseaseName": "supravalvular aortic stenosis",
              "diseaseId": "MONDO:0008504",
              "inheritanceMode": null,
              "source": "GENCC"
            }
          ],
          "symbol": "ELN",
          "proteinCoding": true,
          "maneSelectEnsemblId": "ENST00000252034.12",
          "maneSelectRefSeqId": "NM_000501.4",
          "lof_pLI": 7.2698e-10,
          "lof_oe_ci_upper": 0.697,
          "decipherHi": 0.0862,
          "clingenHi": "SUFFICIENT_EVIDENCE",
          "clingenHiDisease": "MONDO:0008504",
          "clingenTs": "NO_EVIDENCE_AVAILABLE"
        },
        "overlappedGenePart": {
          "cdsBasesLost": 2175,
          "cdsBasesSize": 2175,
          "cdsFractionLost": 1,
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          "exonsBasesSize": 3397,
          "exonsFractionLost": 1,
          "lostExons": 33,
          "lostExonsRanks": [
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          "readingFrameDestroyed": false,
          "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
          "numberOfPLpVariantsCovered": 118,
          "escapeNmd": false
        },
        "phenotypeHi": "MONDO:0008504",
        "triploinsufficiencyType": "NO_EVIDENCE_AVAILABLE",
        "haploinsufficiencyType": "SUFFICIENT_EVIDENCE"
      },
      {
        "id": "NM_182504.4",
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        "regionType": "GENE",
        "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
        "coveredFraction": 1,
        "hgncId": 23018,
        "geneSummaryLongCarrier": {
          "symbol": "TMEM270",
          "proteinCoding": true,
          "maneSelectEnsemblId": "ENST00000320531.3",
          "maneSelectRefSeqId": "NM_182504.4",
          "lof_pLI": 4.0928e-11,
          "lof_oe_ci_upper": 1.393
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        "overlappedGenePart": {
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          "readingFrameDestroyed": false,
          "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
          "numberOfPLpVariantsCovered": 0,
          "escapeNmd": false
        }
      },
      {
        "id": "NM_152559.3",
        "chr": "7",
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          "proteinCoding": true,
          "maneSelectEnsemblId": "ENST00000297873.9",
          "maneSelectRefSeqId": "NM_152559.3",
          "lof_pLI": 1.7608e-12,
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          "geneGroup": "7BS orphan methyltransferases"
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        "overlappedGenePart": {
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          "readingFrameDestroyed": false,
          "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
          "numberOfPLpVariantsCovered": 0,
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      },
      {
        "id": "NM_001305.5",
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        "regionType": "GENE",
        "overlapType": "FIVE_UTR_WITH_CDS",
        "coveredFraction": 1,
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        "geneSummaryLongCarrier": {
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          "maneSelectRefSeqId": "NM_001305.5",
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      },
      {
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      },
      {
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        "overlappedGenePart": {
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          "readingFrameDestroyed": false,
          "overlapType": "FULL_LAST_EXON_WITH_PREVIOUS_EXONS",
          "numberOfPLpVariantsCovered": 0,
          "escapeNmd": false
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      },
      {
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        "geneSummaryLongCarrier": {
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      },
      {
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            },
            {
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              "diseaseName": "Leber hereditary optic neuropathy, autosomal recessive",
              "diseaseId": "MONDO:0030309",
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      },
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      {
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          "fin_AF": 0.00031,
          "mid_AN": 64,
          "mid_AC": 0,
          "mid_AF": 0,
          "nfe_AN": 58758,
          "nfe_AC": 3,
          "nfe_AF": 0.000051,
          "oth_AN": 1552,
          "oth_AC": 0,
          "oth_AF": 0,
          "sas_AN": 4368,
          "sas_AC": 0,
          "sas_AF": 0
        }
      }
    ]
  },
  "acmg": {
    "position": {
      "chr": "7",
      "start": 72846244,
      "end": 74187855
    },
    "criteria": [
      {
        "criterium": "LOSS_1A",
        "points": 0
      },
      {
        "criterium": "LOSS_2A",
        "points": 1
      },
      {
        "criterium": "LOSS_3B",
        "points": 0.45
      }
    ],
    "criteriaReports": [
      {
        "criterium": "LOSS_1A",
        "report": "The region contains protein-coding genes, for example: EIF4H. The region contains important regions, for example: dbVar:nssv15137072. "
      },
      {
        "criterium": "LOSS_2A",
        "report": "There is complete overlap with established HI region(s): dbVar:nssv15137072, dbVar:nssv15167740, dbVar:nssv17955650, morbid:DNAJC30, dbVar:nssv18791884, dbVar:nssv15770120, dbVar:nssv15147201, dbVar:nssv15140244, dbVar:nssv15130169, dbVar:nssv15128343, morbid:ELN, dbVar:nssv16214500, dbVar:nssv15130113, dbVar:nssv16208140, HI3:ELN, dbVar:nssv17971140, dbVar:nssv16213814, dbVar:nssv18791887, morbid:FKBP6, dbVar:nssv18786274, dbVar:nssv17172746, dbVar:nssv15128578, dbVar:nssv16214480. Among those, regions with breakpoints not laying inside the transcripts: morbid:DNAJC30, morbid:ELN, HI3:ELN, morbid:FKBP6. "
      },
      {
        "criterium": "LOSS_3B",
        "report": "There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, BUD23, STX1A, ABHD11, CLDN3, CLDN4, METTL27, TMEM270, EIF4H"
      }
    ],
    "criteriaData": [
      {
        "criterium": "LOSS_1A",
        "report": "The region contains protein-coding genes, for example: EIF4H. The region contains important regions, for example: dbVar:nssv15137072. ",
        "met": true,
        "points": 0
      },
      {
        "criterium": "LOSS_2A",
        "report": "There is complete overlap with established HI region(s): dbVar:nssv15137072, dbVar:nssv15167740, dbVar:nssv17955650, morbid:DNAJC30, dbVar:nssv18791884, dbVar:nssv15770120, dbVar:nssv15147201, dbVar:nssv15140244, dbVar:nssv15130169, dbVar:nssv15128343, morbid:ELN, dbVar:nssv16214500, dbVar:nssv15130113, dbVar:nssv16208140, HI3:ELN, dbVar:nssv17971140, dbVar:nssv16213814, dbVar:nssv18791887, morbid:FKBP6, dbVar:nssv18786274, dbVar:nssv17172746, dbVar:nssv15128578, dbVar:nssv16214480. Among those, regions with breakpoints not laying inside the transcripts: morbid:DNAJC30, morbid:ELN, HI3:ELN, morbid:FKBP6. ",
        "met": true,
        "points": 1
      },
      {
        "criterium": "LOSS_3B",
        "report": "There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, BUD23, STX1A, ABHD11, CLDN3, CLDN4, METTL27, TMEM270, EIF4H",
        "met": true,
        "points": 0.45
      }
    ],
    "report": "CNV loss of the region 7:72,846,244-74,187,855 (1.3 mb), is localized in (7)(q11.23). The region  contains protein-coding and important regions. There is complete overlap with established HI region(s): dbVar:nssv15137072, dbVar:nssv15167740 (and 21 more). Among those, regions with breakpoints not laying inside the transcripts: morbid:DNAJC30, morbid:ELN (and 2 more). There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50 (and 16 more) in the affected region. ",
    "pathogenicityLevel": "Pathogenic",
    "score": 1.45,
    "svType": "DEL",
    "phenotype": null
  }
}