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Table 1 CHEK2 mutations identified in French women with hereditary breast cancer and a control group of unaffected women

From: CHEK2 contribution to hereditary breast cancer in non-BRCAfamilies

Mutation

Amino acid change

Exon

Protein domain

Splicing effect

Align-GVGD class

SIFT median sequence conservation score

SIFT prediction

PolyPhen-2 prediction

Proposed diagnosis

Case population (n = 13)

         

190G > A [49] (two cases)

Glu64Lys

2

SQ/TQ

-

C15

2.23

Tolerated

Benign

Probably benign

190G > T

Glu64X

2

SQ/TQ

-

-

 

-

-

Probably deleterious

254C > G [23, 41]

Pro85Arg

2

-

-

C0

2.15

Tolerated

Probably damaging

Probably deleterious

349A > G [23]

Arg117Gly

3

FHA

-

C65

2.07

Deleterious

Probably damaging

Probably deleterious

670A > G

Lys224Glu

5

Kinase

-

C0

2.05

Tolerated

Benign

Probably benign

731A > G

Lys244Arg

6

Kinase

-

C0

2.04

Tolerated

Benign

Probably benign

751A > T [23]

Ile251Phe

6

Kinase

-

C0

2.04

Tolerated

Probably damaging

Probably deleterious

846+4_846+7del

-

7

-

Possibly skip exon 7

-

-

-

-

Probably deleterious

1100del (three cases)

Thr367MetfsX15

11

Kinase

-

-

-

-

-

Probably deleterious

1169A > C

Tyr390Ser

11

Kinase

-

C0

2.04

Deleterious

Probably damaging

Probably deleterious

1281C > A

Phe427Leu

12

Kinase

-

C0

2.04

Deleterious

Probably damaging

Probably deleterious

1427C > T [23]

Thr476Met

13

Kinase

-

C0

2.05

Deleterious

Probably damaging

Probably deleterious

Control population (n = 4)

         

116C > T

Ser39Phe

2

SQ/TQ

-

C65

3.10

Deleterious

Benign

Probably deleterious

251A > G

Glu84Gly

2

-

-

C65

2.17

Tolerated

Probably damaging

Probably deleterious

731A > G

Lys244Arg

6

Kinase

-

C0

2.04

Tolerated

Benign

Probably benign

792+1dup

-

6

-

Probably skip exon 6

-

-

-

-

Probably deleterious

Additional mutations tested for kinase function [27]

     

410G > A

Arg137Gln

3

FHA

-

C0

2.22

Tolerated

Benign

Probably benign

433C > T

Arg145Trp

3

FHA

-

C65

2.05

Tolerated

Probably damaging

Probably deleterious

481_483del

Glu161del

4

FHA

-

-

-

-

-

Probably deleterious

539G > A

Arg180His

4

FHA

-

C0

2.04

Tolerated

Probably damaging

Probably deleterious

  1. Align-GVGD, SIFT (Sorting Intolerant From Tolerant) and PolyPhen-2 (Polymorphism Phenotyping v2) software tool scores and splicing effect were calculated. The possible impact of the different mutations on CHEK2 function is proposed. FHA = Forkhead-associated domain.