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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.