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Table 2 Genetic results of UH patients

From: Exome sequencing for diagnosis of congenital hemolytic anemia

Patient ID Gene name Transcript Nucleotide change AA change zygosity references gnomAD allele frequency Polyphen-2 Mutation taster MaxEnt Scan CADD score ACMG class
P21 SPTA1 NM_003126 c.6600 + 5G > T   het no 0 NA NA −62.5% 18.74 VUS
  SPTA1 NM_003126 c.6531-12C > T   het Alpha-Lely polymorphism
rs28525570
25%      
P22 SPTA1 NM_003126 C.2898G > A p.(=) het no 0 NA NA −29.3% 14.2 VUS
  SPTA1 NM_003126 c.6531-12C > T   het Alpha-Lely polymorphism
rs28525570
25%      
P23 ALAS2 NM_000032 c.-258C > G   het Bekri et al 2003
rs140772352
0.54% NA NA NA   VUS
P24 TRPV4 NM_021625 c.1913C > T p.P638L hom No
rs35058636
0.03% (no homozygotes) B DC No effect   VUS
  ADAR NM_001111 c.1586C > T p.P529L het no 0 PD DC No effect   VUS
P25 SEC23B NM_001172745 c.40C > T p.R14W het Russo et al 2011
rs121918222
0.022% PossD DC No effect   P
  SEC23B NM_001172745 c.325G > A p.E109K het Russo et al 2011
Rs121918221
0.023% PD DC No effect   P
P26 HAMP NM_021175 c.49_54del p.L17_L18del het no 0 NA NA No effect   VUS
  HFE NM_000410 c.845G > A p.C282Y het rs1800562 3.37% PD P No effect   P
  CD46 NM_172359 c.402 T > G p.I134M het no 0 PossD P No effect   VUS
P27 CFH NM_00186 c.2850G > T p.Q950H het Mohlin et al 2015
rs149474608
0.39% B P No effect   LB
P28 SEC23B NM_001172745 c.1276G > A p.V426I het Schwartz et al 2009
rs41309927
4.3% B P No effect   VUS
  CDAN1 NM_138477 c.256C > T p.P86S het No
rs543791953
0.052% B P No effect   VUS
P29 SPTA1 NM_003126 c.1688G > A p.R563Q het No
rs202243588
0.11% PD DC Possible new acceptor site 25.1 VUS
  HBB NM_000518 c.20A > T p.E7V het Yes coding for HbS
rs334
0.44% B P   13.8 P
  SPTA1 NM_003126 c.6531-12C > T   het Alpha-Lely polymorphism
rs28525570
      
P30 PIEZO1 NM_001142864 c.1126C > G p.P376A het no 0 B P Possible new acceptor site   VUS
P31 KCNN4 NM_002250 c.1055G > A p.R352H het Rappetti Mauss et al 2015
rs774455945
0 PossD DC No effect   P
  PIEZO1 NM_001142864 c.3629C > T p.A1210V het No
rs761971227
0.006% B DC No effect   LP
  PIEZO1 NM_001142864 c.3629C > T p.A1210V absence        
P32 SPTB NM_001024858 c.[6706C > A;6737C > T] p.[L2236M;A2246V] Het in cis no 0 B/PD DC/P No effect   VUS
  HBB NM_000518 c.20A > T p.E7V het Yes coding for HbS
rs334
0.44% B P   13.8 P
P33 G6PD NM_000402 c.538G > A p.V180I het no 0 PossD DC No effect   VUS
  SPTB NM_001024858 c.6271C > A p.P2091T het No
rs372733273
0.0065% B DC no effect   VUS
P34 HFE NM_000410 c.187C > G p.H63D hom Kaczoeowska-Hac et al 2016
rs1799945
10.83% B P No effect   LB
  ABCG8 NM_022437 c.-27G > A   het no 0 NA NA NA   VUS
  ADAMTS13 NM_139025 c.119C > G p.A40G het No
rs782213090
0.00041% B P    VUS
  ADAMTS13 NM_139025 c.4007G > A p.R1336Q het No
No rs
0.0012% PD P    VUS
P35 SH2B3 NM_005475 c.1A > G p.0? het no 0 NA NA No effect   LP
  SCN9A NM_002977 c.2938G > T p.A980S het no 0 PossD DC No effect   VUS
P36 SPTA1 NM_003126 c.6672A > C p.E2224D hom No
Rs142775522
1.5% no homozygotes PD DC No effect 22.3 VUS
  SLC4A1 NM_000342 c.1199_1225del p.A400_A408del het Wilder et al 2009
rs769664228
0.0047% PD DC    LP
  PIEZO1 NM_001142864 c.1369C > T p.R457C het Russo et al 2018 0 PD DC No effect   LP
  G6PD NM_000402 c.292G > A p.V98M het Vulliamy et al 1988
rs1050828
1.15%      LP
  HBB NM_000518 c.20A > T p.E7V het Yes coding for HbS
rs334
0.44% B P   13.8 P
P37 SPTA1 NM_003126 c.3291G > A p.W1097* het no 0 NA NA NA 42 LP
  SPTA1 NM_003126 c.6531-12C > T   het Alpha-Lely polymorphism
rs28525570
      
  HFE NM_000410 c.187C > G p.H63D hom Kaczoeowska-Hac et al 2016
rs1799945
10.83% B P No effect   LB
P38 CFH NM_00186 c.157C > T p.R53C het Servais et al 2012
rs757785149
0.0014% PD DC No effect   LP
  PIEZO1 NM_001142864 c.4246G > A p.G1416R het No
rs771605269
0.00033% PD DC New cryptic acceptor site   VUS
P39 SPTA1 NM_003126 c.779 T > C p.L260P het Marchesi et al 1987
Rs121918634
0.017% (Afr) PD DC No effect   LP
  SPTA1 NM_003126 c.6531-12C > T   het Alpha-Lely polymorphism
rs28525570
      
P40 ATP11C NM_173694 c.2434C > T p.P812S hem no 0.00055% no hemizygous PD DC No effect   VUS
  ANK1 NM_020476 c.4558G > C p.E1520Q het no 0.0021% B DC No effect 26 VUS
  1. Table 2 Legend: Variants description and classification according to ACMG guidelines as benign likely benign (LB), variant of uncertain significance. (VUS), likely pathogenic (LP) or pathogenic (P). In silico study of missense variations was assessed thanks to Polyphen-2, Mutation taster andCADD score algorithm. HGMD professional and pubmed web interface were used to check for variants description in litterature. Abbreviations: het: heterozygous state; hom: homozygous state; hem: hemizygous state; F: female; M: male; HS: hereditary spherocytosis; gnomAD: genome agregation database https://gnomad.broadinstitute.org; ND: not done; NA: not applicable; DC: disease causing; P: polymorphism; PD: probably damaging; PossD: possibly damaging; B: benign.