Table 4 Functional classification of 10 genes sharing putative pathogenic variants in at least two trios
From: Whole exome sequencing in three families segregating a pediatric case of sarcoidosis
Trios | Gene | Chr. | Position | Variant | QUAL | Depth | Annotation | Reference | SIFT | Polyphen | Alamut | EXaC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Autophagy and Intracellular Trafficking | ||||||||||||
 T1 + T2 (homoz) | Sec16A | 9 | 139368953 | SNP | 28,526 23,786 | 602 430 | c.3115C > T p.Arg1039Cys (NM_014866.1) | rs3812594 | 0.14 | 0.689 * | Class3 Unknown Exon skip? | 0.21 |
 T1 + T3 (homoz) | AP5B1 | 11 | 65,547,333 | SNP | 15,898 27,369 | 187 219 | c.631C > T p.Leu211Phe (NM_138368.4) | rs12146493 | 0 * | 0.999 * | Class 3 Exon skip | 0.29 |
 T1 + T2 (c/het) | RREB1 | 6 | 7231843 7246998 7230680 7247344 | SNP (T1p) SNP (T1 m) SNP (T2p) SNP (T2 m) | 2748 6191 33,331 14,853 | 226 202 371 173 | c.3511G > A p.Asp1171Asn (NM_001003698.3) c.4150G > A p.Gly1384Arg (NM_001003698.3) c.2348G > T p.Gly783Val (NM_001003698.3) c.4496C > A p.Ser1499Tyr (NM_001003698.3) | rs9379084 rs2281833 rs9502564 rs35742417 | 0 * 0.12 0.06 0.01 * | 0.999 * 0 0.156 0.025 | Class3 Unknown Exon skip? nd nd Class3 Unknown Exon skip? | 0.11 0.27 0.44 0.14 |
G-Proteins Regulation | ||||||||||||
 T1 (homoz) | OBSCN | 1 | 228505204 | SNP | 11,933 | 256 | c.16472G > A p.Arg5491His (NM_001271223.2) | rs4653942 | 0 * | 0.91 * | Class3 Unknown | 0.26 |
 T3 (homoz) |  |  | 228494790 | SNP | 39,725 | 479 | c.14986G > A p.Gly4996Arg (NM_001271223.2) | rs435776 | 0.01 * | 0.939 * | Class 3 Unknown | 0.41 |
 T2 (de novo) | CTNND2 | 5 | 10981914 | SNP | 299 | 111 | c.3388G > A p.Ala1130Thr (NM_001332.3) | nd | nd | nd | nd | nd |
 T2 + T3 (c/het) | DNAH11 | 7 | 21893993 | SNP (T2p) | 46,459 | 445 | c.11122G > T p.Val3708Leu (NM_001277115.1 | rs4722064 | 0.02 * | 0.611 * | Class 3 Unknown | 0.43 |
21584693 | SNP (T2 m) | 1610 | 159 | c.421G > T p.Asp141Tyr (NM_001277115.1) | rs72655969 | 0 * | 0.601 * | Class 3 Unknown | 0.012 | |||
21,628,242 | SNP (T3p) | 20,259 | 553 | c.1961C > G p.Ser654Cys (NM_001277115.1) | rs62441683 | 0.67 | 0.02 | Class 3 Unknown | 0.13 | |||
21678643 | SNP (T3 m) | 19,593 | 850 | c.4904A > G p.Asp1635Gly (NM_001277115.1) | rs17144835 | 0 * | 0.783 * | Class 3 Unknown Exon skip? | 0.045 | |||
T-Cell Activation and Immune Synapse | ||||||||||||
 T1 + T3 (c/het) | IDO2 | 8 | 39862881 | SNP (T1p) | 14,321 | 289 | c.742C > T p.Arg248Trp (NM_194294.2) | rs10109853 | 0 * | 1 * | Class 3 Unknown | 0.48 |
39873053 | SNP (T1 m) | 7771 | 184 | c.1195G > A p.Ala399Thr (NM_194294.2) | rs72632016 | 0.57 | 0.024 | Class 3 Unknown | 0.06 | |||
39872935 | SNP (T3p) | 21,240 | 451 | c.1077 T > A p.Tyr359* (NM_194294.2) | rs4503083 | STOP * | STOP * | Truncating Polymorphism | 0.226 | |||
39862893 | SNP (T3 m) | 3510 | 154 | c.754 T > A p.Ser252Thr (NM_194294.2) | rs35212142 | 0.02 * | 0.444 * | Class 3 Unknown | 0.02 | |||
 T1 (de novo) | IGSF3 | 1 | 117122285 | In frame INS | 14,580 | 191 | c.3122_3123insGGA p.Asp1040_1041insGlu (NM_001542.3) | rs114915440 | IF INS | IF INS | In frame polymorphism | 0.25 |
Mitosis and Immune Synapse | ||||||||||||
 T1 (de novo) | SPICE1 | 3 | 113172543 | SNP | 3572 | 291 | c.1912 T > G p.Ser638Ala (NM_144718.3) | nd | nd | nd | Unknown | nd |
 T1 (homoz) | KNL1 (CASC5) | 15 | 40916237 | SNP | 57,541 | 697 | c.3853A > G p.Lys1285Glu (NM_170589.4) | rs17747633 | 0.05 * | 0.058 | Class 3 Unknown Exon skip? | 0.32 |
 T2 (homoz) |  |  | 40915190 | SNP | 183,916 | 368 | c.2806A > G p.Arg936Gly (NM170589.4) | rs8040502 | 1 | 0 | Class 3 Unknown | 0.24 |
 T3 (homoz) |  |  | 40914177 | SNP | 66,997 | 297 | c.1793 T > C p.Met598Thr (NM170589.4) | rs11858113 | 0.01 * | 0.006 | Class3 Unkown | 0.39 |