TABLE 2.
Candidate LOF variants in cohort
| Public database frequencies*
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene | Biologic processes (http://www.uniprot. org) |
dbSNP ID | Position | Codon change |
Allele count |
Amino acid change |
1000 Genomes† |
ExAC‡ | ESP§ |
| MBL2 (mannose-binding protein C) | Calcium-dependent lectin involved in innate immune defense. Binds mannose, fucose, and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. | rs74754826 | chr10: 54528016 | GAG>TAG | 3 | E210X | 0.010 | 0.007 | 0.006 |
| KLRC3 (NKG2-E type II integral membrane protein killer cell lectin-like receptor subfamily C, Member 3) | Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T cells. | rs145456037 | chr12: 10568251 | AAA>TAA | 5 | K244X | 0.046 | 0.058 | NA |
| PCSK5 (proprotein convertase subtilisin/kexin type 5) | Establishment by proteolytic activation of a number of important factors such as alpha-integrins. | rs77068135 | chr9: 78790143 | TGG>TGA | 4 | W666X | NA | 0.036 | NA |
| IDI2 (isopentenyl-diphosphate delta-isomerase 2) | Involved in the biosynthesis of isoprenoids. | rs1044261 | chr10: 1065710 | TGG>TAG | 4 | W144X | 0.038 | 0.046 | 0.047 |
| EPHB2 (ephrin type-B receptor 2) | Receptor tyrosine kinase which binds transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. | rs76826147 | chr1: 23240250 | AAA>TAA | 3 | K1019X | 0.043 | 0.046 | 0.040 |
| C1orf194 (uncharacterized protein) | Unknown | rs62623709 | chr1: 109650558 | TAC>TAA | 3 | Y61X | 0.031 | 0.035 | 0.040 |
*
African population MAFs are shown. Global MAFs for all variants were lower than African MAFs except PCSK5 (global MAF = 0.060).
†
The 1000 Genomes database is the largest public catalog of human variation and genotype data.
‡
Exome Aggregation Consortium (ExAC) comprises of exome sequencing data from 60,706 unrelated individuals participating in various disease-specific and population genetic studies. Individuals affected by severe pediatric disease are excluded so this data set should serve as a useful reference set of allele frequencies for severe disease studies.
§
NHLBI GO Exome Sequencing Project (ESP) comprises of exome sequencing data from various studies of heart, lung, and blood disorders.