Table 1

Summary of phenotypic information in subjects with CC2D2A mutations, single heterozygous variants, and variants of unclear functional significance identified in this cohort

Identification noCC2D2A mutations, cDNACC2D2A mutations, proteinP2 score, Div/VarCtrl allele % EU/AAAge (years)MTSECDD/ IDSzA/TNyst, OMARDKidneyLiverPDOther
CC2D2A mutations and phenotypic summary
 UW36-37c.3364C>T homM,Pp.P1122S1.0/0.9908+++
 UW41-37c.2848C>T homM,Pp.R950X hom04++++Cortic vis imp
 UW46-1 Nc.3289 delGP
c.4289T>CM
p.V1097Ffs*1
p.V1430A
1.0/0.86ND
0
19+++
 UW46-2 Nc.3289 delGP
c.4289T>CM
p.V1097Ffs*1
p.V1430A
1.0/0.86ND
0
22+++Scoliosis
 UW47-37c.3055C>TM
c.3288G>CP
p.R1019X
p.Q1096H
0.64/0.120
0
19+++++
 UW48-37c.3364C>T homM,Pp.P1122S1.0/0.9907*++++++ (ESRF/TXPT)Scoliosis
 UW49-330c.3289 delGM
c.4582C>TP
p.V1097Ffs*1
p.R1528C
1.0/0.97ND
0
24+++++++ (TXPT)Coloboma
COACH
 UW50-37c.4582C>T homM,Pp.R1528C hom1.0/0.97012++Sibling w/ EC
 UW50-67c.4582C>T homM,Pp.R1528C hom1.0/0.9708+++
 UW67-330c.3145C>T
c.3347C>T
p.R1049X
p.T1116M
1.0/0.970
0.03/0
7++++++ fibrosis
 UW75-3Nc.1676T>CM
c.3892_3 del(GT)P
p.L559P
p.V1298Ffs*16
1.0/0.990
ND
18++++
 UW76-3 Nc.3134T>CP
c.3850C>TM
p.V1045A
p.R1284C
0.98/0.6
1.0/1.0
0
0
3+++
 UW78-3 Nc.3055C>TM
c.4667A>TP
p.R1019X
p.D1556V
0.98/0.740
0.03/0.03
1+++NDND
 UW79-3 Nc.(1263_4InsGGCATGTTTTGGC; c.1268G>A)P
c.3452T>CM
p.S423Gfs*19
p.V1151A
1.0/0.39ND
0
0
26++++
 UW79-4 Nc.(1263_4InsGGCATGTTTTGGC; 1268G>A)P
c.3452T>CM
p.S423Gfs*19
p.V1151A
1.0/0.39ND
0
0
24+++++
 UW80-3c.3289 delG
c.3347C>T
p.V1097Ffs*1
p.T1116M
1.0/0.97ND
0.03/0
1++++ND+ (cysts)ND
 UW81-3 Nc.4179+1delG
c.4667A>T
p.E1393Efs*1
p.D1556V
0.98/0.74ND
0.03/0.03
11+++
 UW82-3 Nc.3976-3C>AP
c.4844_4847delCTCTM
p.IVS30(-3)
p.S1615Lfs*15
0
ND
8+++++
 UW102-3 Nc.3772-1G>TP
c.4582C>TM
p.IVS29(-1)
p.R1528C
1.0/0.970
0
4+++NDCortic vis imp
 UW103-3 Nc.3289delG
c.3851G>A
p.V1097Ffs*1
p.R1284H
1.0/1.0ND
0
3++Sibling w/ MKS
 n=20 subjects from 17 families20/201/2020/205/2012/2013/192/204/192/180/19
Single heterozygous changes and variants of unclear significance
 UW06-3 Nc.351T>Gp.S117R0.84/0.360.2/0.0714+++F++++ (ESRF, TXPT)VPI
 UW54-3c.1519A>Gp.K507E0.99/0.700.8/0.0810+++++ (ESRF, TXPT)+ (TXPT)Coloboma
TMEM67
 UW88-3 Nc.3989G>Ap.R1330Q1.0/0.94010+++
 UW88-4 Nc.3989G>Ap.R1330Q1.0/0.94013++
 UW106-3c.4667A>Tp.D1556V0.98/0.740.03/0.034++
 UW107-3c.1519A>Gp.K507E0.99/0.700.8/0.082+++Twins
 UW107-4c.1519A>Gp.K507E0.99/0.700.8/0.082+++
 UW108-3 Nc.3055C>Tp.R1019X01ND+ND++NDNDNDSibling with MTS
 UW109-3 NDc.3347C>Tp.T1116M1.0/0.970.03/02+++NDNDNDND
 UW110-3Nc.2101C>Gp.L701V0.05/0.020<1*+++NDND+ND+
 UW111-3Nc.351T>Gp.S117R0.84/0.360.2/0.072++++ND+Coloboma
TCTN2
UW77-3Nc.1978G>A
c.2050T>A
p.V660I
p.L684I
0.004/0.005
0.003/0.004
0.01/2.4
0/0.5
13+++++
 UW104-3 Nc.685_687delGAA
c.1017+1G>A
p.E229del
p.IVS11(+1)
3/ND
0/0.03
<1+++NDNDDextro-cardia
 UW105-3c.685_687delGAA
c.4667A>T
p.E229del
p.D1556V
0.98/0.743/ND
0.03/0.03
6+++NN++
  • Nonsense or frameshift mutations are in bold. Mutations predicted as benign by Polyphen-2 are italicised. Subjects with CC2D2A mutations of unclear functional significance and single heterozygous CC2D2A variants are listed in the lower part of the table. Control allele frequency is based on exome data (see Methods: Controls). UW50-3 and UW50-6 are first cousins; all other subjects sharing the same UW number are siblings.

  • P, paternal; M, maternal alleles; N, mutation not previously reported.

  • * Deceased.

  • A/T, apnoea/tachypnoea; cortic vis imp, cortical visual impairment; Ctrl allele freq % EU/AA, control allele frequency as percentage in European Americans/African Americans; DD/ID, developmental delay/intellectual disability; del, deletion; EC, encephalocele; ESRF, end stage renal failure; hom, homozygous; F, febrile seizures; MKS, Meckel syndrome; MTS, molar tooth sign; NN, neonatal seizures; ND, not documented; Nyst, nystagmus; OMA, oculomotor apraxia; P2 score, Polyphen-2 scores (both ‘Hdiv and Hvar’ are indicated); PD, polydactyly; RD, retinal dystrophy; Sz, seizures; TXPT, transplant; VPI, velopalatal insufficiency.