Table 3 Mutations in BC/OC susceptibility genes identified and clinical presentation in respective patients

#

Exon

cDNA-change

Predicted AA-change

BIC

GnomAD

Age at diagnosis

Contra-lateral disease

Other cancers

Family BC/OC history

1

2

c.68_69delAG

p.(Glu23Valfs*17)

185delAG

1.987e⁻⁴

46

–

34 y lymphoepithelial cancer

Repeated skin cancer of unknown origin

BC

2

5

c.181 T > G

p.(Cys61Gly)

C61G

3.255e⁻⁵

38

–

–

BC

3

5

c.181 T > G

p.(Cys61Gly)

C61G

3.255e⁻⁵

43

–

36 y/ 42 y basalioma

OC

4

11

c.904delG

p.(Ala302Leufs*12)

1023delG

0

30

–

–

BC, OC

5

11

c.962G > A

p.(Trp321*)

W321X

8.237e⁻⁶

29

–

–

BC 3rd degree relative

6

11

c.1127delA

p.(Asn376Ilefs*18)

1246delA

0

23/23

yes

–

BC

7

11

c.1396delC

p.(Arg466Glyfs*9)

–

0

45

–

–

BC, OC

8

11

c.1504_1508delTTAAA

p.(Leu502Alafs*2)

1623del5

8.135e⁻⁶

40/54

yes

–

BC, OC

9

11

c.1504_1508delTTAAA

p.(Leu502Alafs*2)

1623del5

8.135e⁻⁶

54

–

–

BC, OC

10

11

c.1916 T > A

p.(Leu639*)

L639X

0

34

–

–

BC, OC

11

11

c.1916 T > A

p.(Leu639*)

L639X

0

42

–

–

BC, OC

12

11

c.2411_2412delAG

p.(Gln804Leufs*5)

2530delAG

0

37

–

–

–

13

11

c.2411_2412delAG

p.(Gln804Leufs*5)

2530delAG

0

33

–

–

BC, OC

14

11

c.2411_2412delAG

p.(Gln804Leufs*5)

2530delAG

0

33

–

–

–

15

11

c.2411_2412delAG

p.(Gln804Leufs*5)

2530delAG

0

45/52

yes

–

BC

16

11

c.2411_2412delAG

p.(Gln804Leufs*5)

2530delAG

0

53

–

–

BC

17

11

c.3481_3491del

p.(Glu1161Phefs*3)

3600del11

0

40

–

–

BC, OC

18

11

c.3481_3491del

p.(Glu1161Phefs*3)

3600del11

0

46

–

–

BC, unk. Abd. canc.

19

11

c.3481_3491del

p.(Glu1161Phefs*3)

3600del11

0

65

–

–

–

20

11

c.3627dupA

p.(Glu1210Asnfs*11)

3746ins A

0

59

–

–

BC

21

11

c.3700_3704delGTAAA

p.(Val1234Glnfs*8)

3819del5

0

43/47

yes

–

BC

22

11

c.3700_3704delGTAAA

p.(Val1234Glnfs*8)

3819del5

0

50

–

–

BC, OC

23

11

c.4035delA

p.(Glu1346Lysfs*20)

4154delA

4.066e⁻⁶

43

–

–

BC

24

11

c.4676-1G > A

IVS15-1G > A

0

30/30

yes

–

BC 4th degree relative

25

13–15

Deletion exon 13–15

–

0

58

–

–

BC

26

20

c.5194_5277del

p.(His1732_Lys1759del)

Exon20del

0

32/36

yes

–

BC

27

20

c.5266dupC

p.(Gln1756Profs*74)

5382insC

0

33

–

–

–

28

20

c.5266dupC

p.(Gln1756Profs*74)

5382insC

0

33

–

–

BC, OC

29

20

c.5266dupC

p.(Gln1756Profs*74)

5382insC

0

30/48

yes

–

–

30

20

c.5266dupC

p.(Gln1756Profs*74)

5382insC

0

35

–

–

BC, unk. Abd. canc.

31

20

c.5266dupC

p.(Gln1756Profs*74)

5382insC

0

39

–

–

BC, unk. Abd. canc.

32

21–24

c.5278-?_5592 +?del

Deletion exon 21–24

–

0

33

–

–

BC, unk. Abd. canc.

33

21

c.5291 T > C

p.(Leu1764Pro)

L1764P

0

42

–

–

BC

34

24

c.5492delC

p.(Pro1831Leufs*3)

6511delC

0

45

–

–

BC

1

5

c.516 + 2 T > A

IVS6 + 2 T > A

0

41

–

–

BC

2

10

c.1813dupA

p.(Ile605Argfs*9)

2041ins A

0

29

–

–

BC

3

10

c.1813dupA

p.(Ile605Argfs*9)

2041ins A

0

29

–

–

BC

4

11

c.2244_2245del

p.(Tyr748*)

2472delCA

0

31

–

–

–

5

11

c.5303_5304delTT

p.(Leu1768Argfs*5)

5531delTT

4.075e⁻⁶

42

–

–

OC

6

11

c.5616_5620delAGTAA

p.(Lys1872Asnfs*2)

5844del5

4.126e⁻⁶

42

–

–

–

7

11

c.6486_6489del4

p.(Lys2162Asnfs*5)

6714del4

8.785e⁻⁶

29/33

yes

–

BC 3rd degree relative

8

15

c.7180A > T

p.(Arg2394*)

R2394X

0

51/64

yes

–

BC

9

15

c.7617 + 2 T > G

7829 + 2 T > G

0

53

–

–

BC

10

17

c.7878G > C

p.Trp2626Cys

W2626C

4.064e⁻⁶

63

–

–

BC

11

20

c.8560delT

p.(Tyr2854Metfs*9)

8788delT

0

38/52

yes

–

BC

12

22

c.8755-1G > A

IVS21-1G > A

0

68

–

–

BC, OC

13

23

c.8992_9025del34

p.(Ser2998Ilefs*19)

–

0

60

–

–

–

#

Exon

cDNA-change

Predicted AA-change

ClinVar (number of reported individuals)

GnomAD frequency

Age at diagnosis

Contra-lateral disease

Other cancers

Family BC/OC history

1

7

c.955C > T

p.(Arg319*)

Pathogenic (5)

8.128e⁻⁶

30

–

–

BC

2

8

c.1026 + 5_ + 7delGTA

Likely pathogenic (5)

Pathogenic (1)

0

43

–

64 y non-Hodgkin-lymphoma

BC

3

8

c.1026 + 5_ + 7delGTA

Likely pathogenic (5)

Pathogenic (1)

0

51

–

–

BC, unk. Abd. canc.

1

7

c.577-2A > G

Likely pathogenic (1)

0

52

–

–

–

1

4

c.470 T > C

p.(Ile157Thr)

Likely pathogenic (4)

Pathogenic (7)

Unknown (3)

5.061e⁻³

50

–

–

BC 3rd degree relative

2

4

c.470 T > C

p.(Ile157Thr)

Likely pathogenic (4)

Pathogenic (7)

Unknown (3)

5.061e⁻³

47

yes

–

–

1

6

c.657_661del5p

p.(Lys219Asnfs*16)

Pathogenic (12)

Risk factor (1)

1.988e⁻⁴

56

–

66 y OC

BC

1

26

c.3802delG

p.(Val1268Terfs*1)

Pathogenic (5)

3.972e⁻⁵

40

–

–

–

1

4

c.1227_1231delTGTTA

p.(Tyr409*)

–

0

44

–

25 y melanoma

BC 3rd degree relative

2

11

c.3165C > A

p.(Tyr1055*)

Pathogenic (1)

0

47

–

–

–