Table 1 Predicted pathogenic missense variants defined by the BRCA2 homology-directed repair (HDR) assay

From: Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models

Variant

cDNA

AGVGD class

IARC class

FCa

SE

p (Pathogenicity)

p (Neutrality)

Origin

G2748D

c.8243G>A

C65

Class 5

0.68

 ± 0.07

1.00

2.96E-12

Lindor et al.,19

L2686P

c.8057T>C

C45

 

0.72

 ± 0.04

1.00

9.50E-12

Guidugli et al.,36

L2653P

c.7958T>C

C65

Class 5

0.75

 ± 0.08

1.00

3.40E-11

Lindor et al.,19

E2663K

c.7987G>A

C55

 

0.83

 ± 0.01

1.00

4.00E-10

Current study

R3052W

c.9154C>T

C65

Class 5

0.86

 ± 0.09

1.00

9.33E-10

Lindor et al.,19

L2721H

c.8162T>A

C25

 

0.88

 ± 0.10

1.00

1.70E-09

Guidugli et al.,36

Y2624D

c.7870T>G

C65

 

0.88

 ± 0.06

1.00

1.75E-09

Current study

Y2624H

c.7870T>C

C65

 

0.89

 ± 0.31

1.00

2.40E-09

Current study

L3125R

c.9374T>G

C65

 

0.91

 ± 0.00

1.00

3.41E-09

Current study

R2784W

c.8350C>T

C65

 

0.91

 ± 0.10

1.00

3.88E-09

Guidugli et al.,36

A2603P

c.7807G>C

C25

 

0.92

 ± 0.60

1.00

4.78E-09

Guidugli et al.,36

N3124I

c.9371A>T

C65

Class 4

0.92

 ± 0.10

1.00

4.65E-09

Guidugli et al.,6

L2647P

c.7940T>C

C65

Class 4

0.93

 ± 0.10

1.00

5.79E-09

Lindor et al.,19

S2670L

c.8009C>T

C15

 

0.93

 ± 0.07

1.00

6.20E-09

Guidugli et al.,36

G3076E

c.9227G>A

C65

 

0.95

 ± 0.10

1.00

1.02E-08

Guidugli et al.,36

Y2624N

c.7870T>A

C65

 

0.95

 ± 0.00

1.00

1.20E-08

Current study

L3125H

c.9374T>A

C65

 

0.96

 ± 0.07

1.00

1.36E-08

Guidugli et al.,36

L2510P

c.7529T>C

C65

 

0.98

 ± 0.11

1.00

2.61E-08

Guidugli et al.,36

K2630Q

c.7888A>C

C45

 

0.98

 ± 0.08

1.00

2.49E-08

Guidugli et al.,36

R2824G

c.8470A>G

C65

 

1.00

 ± 0.20

1.00

3.72E-08

Current study

H2623R

c.7868A>G

C25

 

1.00

 ± 0.04

1.00

3.59E-08

Guidugli et al.,36

D2723H

c.8167G>C

C65

Class 5

1.00

 ± 0.01

1.00

3.81E-08

Lindor et al.,19

N2781I

c.8342A>T

C65

 

1.00

 ± 0.10

1.00

4.08E-08

Current study

I2627F

c.7879A>T

C15

Class 5

1.01

 ± 0.08

1.00

4.83E-08

Lindor et al.,19

A2730P

c.8188G>C

C0

 

1.01

 ± 0.01

1.00

5.46E-08

Current study

L2688P

c.8063T>C

C65

Class 4

1.02

 ± 0.08

1.00

5.80E-08

Guidugli et al.,6

G3076R

c.9227G>T

C65

 

1.03

 ± 0.08

1.00

8.66E-08

Guidugli et al.,36

G3076V

c.9226G>C

C65

 

1.03

 ± 0.11

1.00

8.08E-08

Guidugli et al.,36

D2723V

c.8168A>T

C65

 

1.04

 ± 0.08

1.00

1.01E-07

Guidugli et al.,36

W2788R

c.8362T>C

C25

 

1.05

 ± 0.08

1.00

1.37E-07

Guidugli et al.,36

D2723A

c.8168A>C

C65

 

1.06

 ± 0.11

1.00

1.49E-07

Guidugli et al.,36

W2788S

c.8363G>C

C35

 

1.06

 ± 0.08

1.00

1.44E-07

Guidugli et al.,36

N3124K

c.9372C>A

C65

 

1.07

 ± 0.06

1.00

1.89E-07

Current study

G2609V

c.7826G>T

C65

 

1.07

 ± 0.08

1.00

2.24E-07

Guidugli et al.,36

F2642S

c.7925T>C

C45

 

1.07

 ± 0.08

1.00

2.02E-07

Guidugli et al.,36

D3095E

c.9285C>G

C35

Class 4

1.07

 ± 0.12

1.00

1.89E-07

Guidugli et al.,6

T2722R

c.8165C>G

C65

Class 5

1.08

 ± 0.08

1.00

2.78E-07

Lindor et al.,19

G2508R

c.7522G>C

C65

 

1.09

 ± 0.15

1.00

2.92E-07

Current study

S2691F

c.8072C>T

C0

 

1.10

 ± 0.06

1.00

4.09E-07

Guidugli et al.,36

E3002K

c.9004G>A

C55

 

1.10

 ± 0.08

1.00

4.35E-07

Guidugli et al.,36

D2723G

c.8168A>G

C65

Class 5

1.11

 ± 0.12

1.00

5.19E-07

Lindor et al.,19

W2626R

c.7876T>C

C65

 

1.12

 ± 0.01

1.00

6.04E-07

Current study

G2596E

c.7787G>A

C65

 

1.12

 ± 0.09

1.00

5.77E-07

Guidugli et al.,36

Q2561P

c.7682A>C

C15

 

1.13

 ± 0.06

1.00

7.81E-07

Guidugli et al.,36

V2687F

c.8059G>T

C0

 

1.14

 ± 0.02

1.00

8.96E-07

Current study

H2623Y

c.7867C>T

C65

 

1.15

 ± 0.01

1.00

1.32E-06

Current study

W2626C

c.7878G>C

C65

Class 5

1.16

 ± 0.13

1.00

1.56E-06

Lindor et al.,19

G2793R

c.8377G>A

C65

 

1.18

 ± 0.09

1.00

2.23E-06

Guidugli et al.,36

A3028P

c.9082G>C

C0

 

1.18

 ± 0.04

1.00

2.48E-06

Current study

L2792P

c.8375T>C

C65

 

1.19

 ± 0.09

1.00

3.03E-06

Guidugli et al.,36

G2793E

c.8378G>A

C65

 

1.19

 ± 0.07

1.00

2.71E-06

Guidugli et al.,36

A2786P

c.8356G>C

C0

 

1.23

 ± 0.09

1.00

5.97E-06

Guidugli et al.,36

R2784Q

c.8351G>A

C35

 

1.27

 ± 0.14

1.00

1.46E-05

Guidugli et al.,36

G2596R

c.7786G>C

C65

 

1.28

 ± 0.10

1.00

1.73E-05

Guidugli et al.,36

G2585R

c.7753G>A

C65

 

1.30

 ± 0.10

1.00

2.47E-05

Guidugli et al.,36

G3003E

c.9008G>A

C65

 

1.33

 ± 0.08

1.00

4.59E-05

Guidugli et al.,36

G2609D

c.7826G>A

C65

Class 4

1.35

 ± 0.07

1.00

6.19E-05

Guidugli et al.,6

W2725L

c.8174G>T

C55

 

1.35

 ± 0.10

1.00

6.73E-05

Guidugli et al.,36

K2498E

c.7492A>G

C55

 

1.36

 ± 0.10

1.00

7.98E-05

Guidugli et al.,36

Q2655R

c.7964A>G

C35

 

1.38

 ± 0.09

1.00

1.13E-04

Guidugli et al.,36

Y2726C

c.8177A>G

C65

 

1.49

 ± 0.16

1.00

7.86E-04

Guidugli et al.,36

Q2925K

c.8773C>A

C45

 

1.51

 ± 0.12

1.00

1.07E-03

Guidugli et al.,36

D3073G

c.9218A>G

C65

 

1.52

 ± 0.12

1.00

1.17E-03

Guidugli et al.,36

R2659G

c.7975A>G

C65

 

1.57

 ± 0.12

1.00

2.57E-03

Guidugli et al.,36

Y2624C

c.7871A>G

C65

 

1.57

 ± 0.05

1.00

2.71E-03

Current study

R2842P

c.8525G>C

C65

 

1.59

 ± 0.05

1.00

3.40E-03

Current study

D2611G

c.7832A>G

C65

 

1.61

 ± 0.12

0.99

5.09E-03

Guidugli et al.,36

Y2660D

c.7978T>G

C65

 

1.61

 ± 0.12

0.99

5.03E-03

Guidugli et al.,36

N2622S

c.7865A>G

C45

 

1.63

 ± 0.13

0.99

6.76E-03

Current study

  1. cDNA complementary DNA, SE standard error
  2. aFold change in GFP positive cells in HDR assay
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