ClinVar

To identify a prostate cancer susceptibility gene in the 17q21-q22 region (HPC9; 610997), Ewing et al. (2012) sequenced 2,009 exons from 202 genes in germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. They then tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations. Probands from 4 families were discovered to have a rare but recurrent mutation, G84E (rs138213197), in HOXB13. All 18 men with prostate cancer and available DNA in these 4 families carried the mutation. At the time of the analysis the G84E mutation was not reported in dbSNP or in the NCBI 1000 Genomes sequencing project (May 2011), which included 1,094 subjects, 381 of European descent. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5,083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1,401 control subjects (0.1%) (P = 8.5 x 10(-7)). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P = 2.0 x 10(-6)).

Hamosh (2018) noted that the G84E mutation in the HOXB13 gene was present in 530 of 275,718 alleles and in 2 homozygotes in the gnomAD database (October 23, 2018).