{
  "abstract": "Biallelic pathogenic variants in ATM cause ataxia-telangiectasia, while heterozygous carriers may have increased risks of certain cancers. Truncating variants and the recurrent missense variant c.7271T>G are associated with higher cancer risks, compared to other, non-truncating variants. Current risk models do not distinguish between variant types, and the survival benefit of risk-reducing interventions in carriers remains uncertain. Interpretation of missense variants imposes a disproportionate demand on laboratory resources relative to clinical utility.To optimise use of NHS capacity, the UK Cancer Genetics Group (UKCGG) and the Cancer Variant Interpretation Group–UK (CanVIG-UK) Steering and Advisory Group (CStAG) have developed guidance for ATM variant reporting under cancer indications. Diagnostic testing should be restricted to canonical protein-truncating variants and c.7271T>G. Targeted constitutional testing for additional variants ascertained under other indications may be considered where robust evidence supports loss of function, aberrant splicing, or a significant cancer association (odds ratio >2.0, lower confidence interval >1.5). Reports should clearly state evidentiary basis and highlight uncertainties regarding cancer risk and utility of cascade testing. As maintenance of a formal whitelist is not feasible, evidence should be submitted to the CanVar-UK database.This framework prioritises variants with the greatest clinical utility, supporting consistent and equitable genomic practice.",
  "authors": [
    {
      "affiliations": [
        "Royal Marsden NHS Foundation Trust, London",
        "Institute of Cancer Research, London"
      ],
      "name": "Terri McVeigh"
    },
    {
      "affiliations": [
        "St George’s University Hospital, London"
      ],
      "name": "K Snape"
    },
    {
      "affiliations": [
        "Royal Devon University Healthcare NHS Foundation Trust, Exeter"
      ],
      "name": "H Hanson"
    },
    {
      "affiliations": [
        "Sheffield Children’s NHS Foundation Trust, Sheffield"
      ],
      "name": "M Durkie"
    },
    {
      "affiliations": [
        "St George’s University Hospital, London"
      ],
      "name": "B Frugtniet"
    },
    {
      "affiliations": [
        "Institute of Cancer Research, London",
        "St George’s University Hospital, London"
      ],
      "name": "A Garrett"
    },
    {
      "affiliations": [
        "Institute of Cancer Research, London"
      ],
      "name": "S Allen"
    },
    {
      "affiliations": [
        "Royal Marsden NHS Foundation Trust, London",
        "Institute of Cancer Research, London"
      ],
      "name": "C Turnbull"
    }
  ],
  "title": "P31 UK guidance for analysis and reporting of ATM variants ascertained through cancer indications",
  "uid": "81b172d0-dbe8-50db-b065-eb390d77b8f6"
}