Table 2.

Risk of developing second primary breast cancer associated with rare ATM variants

ATM variant classificationCases (n)Controls (n)Rate ratio * (95% CI)
A-T–causing mutations
    A-T–causing 14131.4 (0.6–3.4)
Variants of unknown effect classified by SIFT
    Deleterious39561.3 (0.8–2.2)
    Tolerated36720.9 (0.6–1.4)
  • * Adjusted for exact age at diagnosis of the first primary, countermatching weight and for carriers of the other remaining ATM variants.

  • Meeting one or more of the following criteria: (a) changes predicted to result in truncation of the ATM protein whether by direct termination or frameshifting, (b) changes affecting the two highly conserved nucleotides flanking exons that direct splicing, (c) changes predicted to result in amino acid substitutions for which there is documented evidence of both a deleterious effect on ATM function and identification in diagnosed A-T patients, or (d) changes documented as A-T–causing in the ATM Mutation Database.

  • Defined by SIFT. Variants with normalized probabilities <0.05 are predicted to be deleterious, whereas those ≥0.05 are predicted to be tolerated. Results for missense variants are adjusted for other variants.