{
  "abstract": "Clinical diagnostic genome sequencing (GS) pipelines typically focus on small and copy number variants since detection and interpretation of other types of structural variant (SV) are more challenging. Reanalysis applying additional methods increases diagnostic yield. Therefore, SV detection provides an opportunity to identify new diagnoses through ongoing Diagnostic Discovery analysis.SV analysis was carried out using GS data for 5,526 undiagnosed probands with a primary neurodevelopmental phenotype. Rare SVs impacting genes associated with intellectual disability in PanelApp in which truncating variants are associated with a dominant disorder were prioritised. SV types included were insertions, breakends, and deletions or duplications not detected by read-depth.Twenty-two SVs were identified impacting targeted genes: ten deletions, seven balanced translocations, four inversions and one complex balanced rearrangement. Deletions include six less than 2 kb impacting a single exon and two mosaic variants. Twelve balanced SVs disrupted ten genes, with eleven SVs resulting in loss of function and one anticipated to have a dominant negative impact. Two SVs had multiple breakpoints.SV detection is anticipated to improve with long-read sequencing. However, incorporating SV analysis into short-read reanalysis workflows expands the utility of existing data and provides timely new diagnoses for families.",
  "authors": [
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "Susan Walker"
    },
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "C Smith"
    },
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "N Elkhateeb"
    },
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "J Lipecki"
    },
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "A Bennett"
    },
    {
      "affiliations": [
        "NHS England, London"
      ],
      "name": "R Mein"
    },
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "E Thomas"
    },
    {
      "affiliations": [
        "Genomics England, London"
      ],
      "name": "H Brittain"
    }
  ],
  "title": "P35 Increasing the diagnostic yield in neurodevelopmental disorders with structural variant analysis",
  "uid": "7f9e2dd4-84c7-5507-a322-349655ef2853"
}