Table 1 Pathogenic/likely pathogenic germline variants in CDKN2A affecting p16^INK4A, p14^ARF transcripts and the associated neoplasms reported in the literature

Ex 1β

Del of Exon 1

–

null

–

–

–

–

/

uterine adenocarcinoma, thyroid adenomata, chest wall neurilemmoma, pituitary macroadenoma

[21, 25]

Ex 1β

c.47G > A

Gly16Asp

MS

–

–

–

–

/

[20]

Ex 1β

c.60_61insCGGCCCGCCGCGAGTG

Val22Profs*46

PT

–

–

–

–

/

[19]

Ex 1β

c.97dup

Glu33Glyfs*30

PT

–

–

–

–

Bladder ca.

[26]

Ex 1β

c.161G > A

Arg54His

MS

–

–

–

–

/

[27]

Ex 1β

c.193G > C

Gly65Arg

MS

–

–

–

–

/

/

[25, 28, 29]

In 1

c.193 + 1G > A

n.d.

Splice^a

–

–

–

–

/

[25, 27, 29,30,31]

In 1

c.194-3653G > T

n.d.

Int

Ex 1α

c.-34G > T

–

5’UTR

/

[25, 29, 32,33,34,35]

In 1

c.194-3635dup

n.d.

Int

Ex 1α

c.-16_8dup

Ala4_Pro11dup ^b

In-frame INS

/

Multiple myeloma, brain tumor, colorectal ca.

[14, 36,37,38,39,40]

In 1

c.194-3585C > A

n.d.

Int

Ex 1α

c.35C > A

Ser12*

PT

/

[41, 42]

In 1

c.194-3576G > A

n.d.

Int

Ex 1α

c.44G > A

Trp15*

PT

/

[25, 35, 42,43,44]

In 1

c.194-3573 T > G

n.d.

Int

Ex 1α

c.47 T > G

Leu16Arg

MS

/

/

[4, 25, 29, 45, 46]

In 1

c.194-3573 T > C

n.d.

Int

Ex 1α

c.47 T > C

Leu16Pro

MS

/

/

[9, 45,46,47,48]

In 1

c.194-3553G > A

n.d.

Int

Ex 1α

c.67G > A

Gly23Ser

MS

/

[45]

In 1

c.194-3552G > A

n.d.

Int

Ex 1α

c.68G > A

Gly23Asp

MS

/

[25, 48,49,50,51]

In 1

c.194-3549G > C

n.d.

Int

Ex 1α

c.71G > C

Arg24Pro

MS

/

/

/

[25, 32, 34, 51,52,53]

In 1

c.194-3541G > T

n.d.

Int

Ex 1α

c.79G > T

Glu27*

PT

/

Neuroblastoma

[25, 54, 55]

In 1

c.194-3525 T > C

n.d.

Int

Ex 1α

c.95 T > C

Leu32Pro

MS

/

/

/

[18, 25]

In 1

c.194-3514delG

n.d.

Int

Ex 1α

c.106delG

Ala36Argfs*17

PT

/

/

[15]

In 1

c.194-3489_194-3488insAA

n.d.

Int

Ex 1α

c.131_132insAA

Tyr44*

PT

/

[56,57,58]

In 1

c.194-3488C > G

n.d.

Int

Ex 1α

c.132C > G

Tyr44*

PT

/

[56,57,58]

In 1

c.194-3488del

n.d.

Int

Ex 1α

c.132del

Tyr44*

PT

/

/

[59]

In 1

c.194-3478C > A

n.d.

Int

Ex 1α

c.142C > A

Pro48Thr

MS

/

[25]

In 1

c.194-3477C > T

n.d.

Int

Ex 1α

c.143C > T

Pro48Leu

MS

/

[60]

In 1

c.194-3474 T > G

n.d.

Int

Ex 1α

c.146 T > G

Ile49Ser

MS

/

/

/

[18, 25]

In 1

c.194-3472C > T

n.d.

Int

Ex 1α

c.148C > T

Gln50* ^c

PT

/

/

[32]

In 1

c.194-3471A > C

n.d.

Int

Ex 1α

c.149A > C

Gln50Pro

MS

/

[52]

In 1

c.194-69C > T

n.d.

Int

In 1

c.151-69C > T

–

Int

/ (Uvl)

[61]

In 1

c.194-2A > G

n.d.

Splice

In 1

c.151-2A > G

n.d.

Splice

/

[18]

In 1

c.194-1G > C

n.d.

Splice^a

In 1

c.151-1G > C

n.d.

Splice^a

/

/

/

/

Osteochondroma

[11, 13, 62]

Ex 2

c.202G > C

Asp68His

MS

Ex 2

c.159G > C

Met53Ile

MS

/

[32, 34]

Ex 2

c.202G > A

Asp68Asn

MS

Ex 2

c.159G > A

Met53Ile

MS

/

/

[32]

Ex 2

c.210G > T

Gln70His

MS

Ex 2

c.167G > T

Ser56Ile

MS

/

[34, 35, 48, 63,64,65]

Ex 2

c.215C > T

Pro72Leu

MS

Ex 2

c.172C > T

Arg58* ^d

PT

/

[25]

Ex 2

c.219 T > G

Ser73Arg

MS

Ex 2

c.176 T > G

Val59Gly

MS

/

[4, 30, 33, 48, 64, 66,67,68]

Ex 2

c.237 T > C

Ala79=

Silent

Ex 2

c.194 T > C

Leu65Pro

MS

/

[18, 25]

Ex 2

c.245_246delinsTT

Arg82Leu

MS

Ex 2

c.202_203delinsTT

Ala68Leu

MS

/

/

[25]

Ex 2

c.255A > G

Gln85=

Silent

Ex 2

c.212A > G

Asn71Ser

MS

/

[4, 59, 69, 70]

Ex 2

c.256C > A

Leu86Met

MS

Ex 2

c.213C > A

Asn71Lys

MS

/

/

/

Multiple myeloma

[17, 25]

Ex 2

c.262C > T

Arg88*

PT

Ex 2

c.219C > T

Ala73=

Silent

Stomach ca.

[26]

Ex 2

c.268_286del / c.269_287del

Arg90Valfs*76

PT

Ex 2

c.225_243del / c.226_244del

Ala76Cysfs*64 ^e

PT

/

/

/

Uterine carcinomasarcoma

[18, 25, 32, 44, 71,72,73,74,75,76]

Ex 2

c.283_296del

Thr95Leufs*61

PT

Ex 2

c.240_253del

Pro81Cysfs*34

PT

/

/

/

Papillary thyroid ca., uterine tumors

[77]

Ex 2

c.302C > T

Pro101Leu

MS

Ex 2

c.259C > T

Arg87Trp

MS

/

[33, 55, 63, 78, 79]

Ex 2

c.303G > C

Pro101=

Silent

Ex 2

c.260G > C

Arg87Pro

MS

/

/

/

[10, 25, 69, 80]

Ex 2

c.305G > T

Gly102Val

MS

Ex 2

c.262G > T

Glu88*

PT

/

[33, 81]

Ex 2

c.326del

Gly109Valfs*63

PT

Ex 2

c.283del

Val95Trpfs*51

PT

/

[46]

Ex 2

c.451_454dupGGTG

Ala152Glyfs*51

PT

Ex 2

c.285_288dupGGTG

Leu97Glyfs*24

PT

/

Low grade neuroepithelial tumor

[53]

Ex 2

c.339G > C

Pro113=

Silent

Ex 2

c.296G > C

Arg99Pro

MS

/

/

[25]

Ex 2

c.344G > T

Arg115Leu

MS

Ex 2

c.301G > T

Gly101Trp

MS

/

/

[18, 25, 32, 33, 67]

Ex 2

c.350_351del

Ala117Glyfs*43

PT

Ex 2

c.307_308del

Arg103Alafs*16

PT

/

[25, 34]

Ex 2

c.365G > T

Arg122Leu

MS

Ex 2

c.322G > T

Asp108Tyr

MS

/

[82]

Ex 2

c.377C > G

Pro126Arg

MS

Ex 2

c.334C > G

Arg112Gly

MS

/

[25]

Ex 2

c.378_380dup

Ser127dup

In-frame INS

Ex 2

c.335_337dup

Arg112dup ^f

In-frame INS

/

/

/

non-Hodgkin’s lymphoma, cervical ca., phyllodes tumor

[10, 25]

Ex 2

c.382_383delinsCT

Ala128Leu

MS

Ex 2

c.339_340delinsCT

Pro114Ser

MS

/

[63]

Ex 2

c.383_398del

Ala128Glufs*39

PT

Ex 2

c.340_355del

Pro114Argfs*27

PT

/

[83]

Ex 2

c.*2del

–

3’UTR

Ex 2

c.358del

Glu120Serfs*26

PT

/

/

/

[25, 67]

Ex 2

c.*21 T > A

–

3’UTR

Ex 2

c.377 T > A

Val126Asp

MS

/

/

[4, 9, 32, 48, 69, 76]

Ex 2

c.*23G > C

–

3’UTR

Ex 2

c.379G > C

Ala127Pro

MS

/

/

[52, 55, 84, 85]

Ex 2

c.*101G > T

–

3’UTR

Ex 2

c.457G > T

Asp153Tyr

MS

/

/

[32]

In 2

c.*102-105A > G

n.d.

3’UTR

In 2

c.458-105A > G

n.d.

Int

/

[25]

Del part of Exon 2

n.d.

PT

Del of Exon 1 & part of Exon 2

/

[86]

Del of entire CDS

–

Del of entire CDS

/

/

/

/

GBM, astrocytoma, meningioma

[12, 16]