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Table 2 Mutations and likely deleterious variants, their effect on splicing or protein, cancer history of carriers

From: Germline mutation in the RAD51B gene confers predisposition to breast cancer

Gene Genetic variation Variant class Effect on splicing Predicted effect on protein (Align-GVGD class) Personal cancer history (age at diagnosis) Family cancer history (age at diagnosis) Controls
RAD51B c.452 + 3A > G Splicing mutation Exon 5 skipping by in silico prediction* Unstable or truncated protein, confirmed by negative IHC BC (34) Paternal aunt, BC (58); 3rd degree relative, OC (29) -
RAD51B c.475C > T, p. Arg159Cys Likely deleterious missense variant No predicted effect ATP-binding domain, highly conserved amino acid, Grantham 180 (Class C65) BC (54) Sister, BC (45); Sister’s daughter BC (45) 2/4299
RAD51C c.706-2A > G Splicing mutation Exon 5 skipping confirmed by mRNA analysis 44 amino acids loss in ATP-binding domain BC (39) Paternal aunt§, OC (67) -
RAD51C c.1026 + 5_1026 + 7del Splicing mutation Exon 8 skipping confirmed by mRNA analysis Unstable or truncated protein BC (38), OC (51) Father, PC (69); Paternal grandmother, UC (66); Paternal grandfather, SC (69) -
XRCC3 c.448C > T, p. Arg150Cys Likely deleterious missense variant No predicted effect ATP-binding domain, highly conserved amino acid, Grantham 180 (Class C65) BC (63) Mother, OC (61); Maternal aunt, BC (55); Maternal aunt, BC (73); Maternal aunt, BC (76); Maternal aunt, BC (63, 79) 1/4276
  1. BC: Breast cancer, OC: Ovarian cancer, PC: Pancreas cancer, UC: Uterine cancer, SC: Stomach cancer.
  2. *See text for details.
  3. †Align-Grantham Variation Grantham Deviation (Align-GVGD) classes range from C0 to C65; C65 class variants are the most likely to interfere with protein function [22, 23].
  4. §This paternal aunt also carried the RAD51C c.706-2A > G mutation.
  5. ‡Frequency in controls in online databases: Exome Variant Server [28], dbSNP [38], 1000 Genomes [29]. The three splicing mutations have never been described. The 2 missense variants were reported only in Exome Variant Server, in European-American populations. Their frequencies in European-American populations are reported in this table.