Introduction
Methods
Patient recruitment and clinical characterization
Patient ID | Clinical Diagnosis | Gene | HumanGRCh37/hg19 | Sequence | cDNA change | Region | ZYG | Protein variant | exaC | gnomAD | Reference | ACMG Classification | Solved patients |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
K4 | Polycystic kidney disease | PKD1 | chr16:2158886 | NM_000296 | c.6282G>A | EX15 | het | p.W2094X | 0 | 0 | This study | Pathogenic | x |
K5 | Polycystic kidney disease | PKD1 | chr16:2143910 | NM_000296 | c.10720_10721insAGGG | EX36 | het | p.W3574Rfs*5 (0 53?) | 0 | 0 | This study | Pathogenic | x |
K6 | Polycystic kidney disease | PKD1 | chr16:2140418 | NM_000296 | c.12307_12308delGT | EX45 | het | p.V4103Yfs*52 | 0 | 0 | This study | Pathogenic | x |
K9 | Polycystic kidney disease | None | |||||||||||
K10 | Polycystic kidney disease | None | |||||||||||
K13 | Polycystic kidney disease | None | |||||||||||
K14 | Polycystic kidney disease | PKD2 | chr4:88973292 | NM_000297 | c.1698_1699insT | EX8 | het | p.V569Cfs*4 | 0 | 0 | [11] | Pathogenic | x |
K15 | Polycystic kidney disease | PKD2 | chr4:88973292 | NM_000297 | 1698_1699insT | EX8 | het | p.V569Cfs*4 | 0 | 0 | [11] | Pathogenic | x |
K25 | Polycystic kidney disease | PKD1 | chr16:2140418 | NM_000296 | c.12307_12308delGT | EX45 | het | V4103fs*52 | 0 | 0 | This study | Pathogenic | x |
K28 | Polycystic kidney disease | PKD1 | chr16:2160078 | NM_000296 | c.5090T>G | EX15 | het | p.L1697R | 0 | 0 | This study | Likely pathogenic | x |
PKD1 | chr16:2157957 | NM_000296 | c.6992C>G | EX16 | Het | p.A2331G | 0 | 0.000109 | This study | Likely benign | |||
K31 | Polycystic kidney disease | PKD1 | chr16:2141795 | NM_000296 | c.11521T>C | EX41 | het | p.W3841R | 0 | 0 | [12] | Likely pathogenic | x |
PKD1 | chr16:2157957 | NM_000296 | c.6992C>G | EX16 | het | p.A2331G | 0 | 0.000109 | This study | Likely benign | |||
K33 | Polycystic kidney disease | PKD1 | chr16:2160232 | NM_000296 | c.4935delC | EX15 | het | p.T1646Pfs*76 | 0 | 0 | [11] | Pathogenic | x |
K34 | Polycystic kidney disease | PKD1 | chr16:2147246 | NM_000296 | c.10403-4C > T | IVS33 | het | Non coding variant | 0.001199 | 0.000467 | [13] | Benign | |
K44 | Polycystic kidney disease | PKD1 | chr16:2160991 | NM_000296 | c.4177C>T | EX15 | het | p.Q1393X | 0 | 0 | [14] | Pathogenic | x |
K54 | Polycystic kidney disease | None | |||||||||||
K56 | Polycystic kidney disease | PKD1 | chr.16:2141032 | NM_001009944 | c.11856C>G | EX43 | het | p.R3952R | − 1 | 0 | This study | likely benign | |
PKD1 | chr16:2154478 | NM_000296 | c.8161+21T>C | IVS22 | hom | Non coding variant | 0.6267 | 0.627 | [15] | Benign | |||
PKD1 | chr16:2164211 | NM_001009944 | c.2813C>T | EX11 | het | p.T938M | 0.1033 | 0.0328 | This study | Uncertain significance | |||
PKD1 | chr16:2165395 | NM_001009944 | c.2081C>T | EX10 | het | p.P694L | 0.1114 | 0.0243 | This study | Uncertain significance | |||
PKD2 | chr4:88928968 | NM_000297 | c.83G>C | EX1 | het | p.R28P | 0.1538 | 0.377 | [13] | Benign | |||
PKD2 | chr4:88959381 | NM_000297 | c.844-22G>A | IVS3 | hom | Non coding variant | 0.6039 | 0.604 | [16] | Benign | |||
K57 | Polycystic kidney disease | PKD1 | chr16:2,158,869 | NM_000296 | c.6299C>T | EX15 | het | p.S2100L | 0.0003206 | 0.0000881 | [17] | Uncertain significance | |
K60 | Polycystic kidney disease | None | |||||||||||
K62 | Polycystic kidney disease | PKD1 | chr16:2153756 | NM_000296 | c.8302G>A | EX23 | het | p.V2768M | 0 | 0.0000081 | [18] | Uncertain significance | |
PKD2 | chr4:88967919 | NM_000297 | c.1445T>G | EX6 | het | p.F482C | 0.002117 | 0.00204 | This study | Benign | |||
K66 | Polycystic kidney disease | None | |||||||||||
K67 | Polycystic kidney disease | PKD1 | chr16:2160622 | NM_000296 | c.4546G>A | EX15 | het | p.A1516T | 0.006088 | 0.00576 | [13] | Benign | |
K70 | Polycystic kidney disease | PKD1 | chr16:2152434 | NM_000296 | c.9149_9150insG | EX25 | het | p.A3050fs | 0 | 0 | This study | Pathogenic | x |
PKD1 | chr16:2153345 | NM_000296 | c.8713G>A | EX23 | het | p.V2905I | 0.001499 | 0.0017 | [18] | Benign | |||
K71 | Polycystic kidney disease | PKD1 | chr16:2154537 | NM_000296 | c.8123C>T | EX22 | het | p.T2708M | 0.006665 | 0.00968 | [18] | Uncertain significance | |
K72 | Polycystic kidney disease | PKD1 | chr16:2150039 | NM_000296 | c.9746T>C | EX29 | het | p.L3249P | 0 | 0 | This study | Uncertain significance | |
PKD1 | chr16:2161666 | NM_000296 | c.3502C>G | EX15 | het | p.P1168A | 0 | 0.0000272 | This study | Likely benign | |||
K76 | Polycystic kidney disease | PKD1 | chr16:2159259 | NM_000296 | c.5909C>G | EX15 | het | p.A1970G | 0 | 0 | This study | Uncertain significance | |
K81 | Polycystic kidney disease | PKD1 | chr16:2159653 | NM_000296 | c.5515T>A | EX15 | het | p.W1839R | 0 | 0 | This study | Likely pathogenic | x |
K82 | Polycystic kidney disease | PKD1 | chr16:2143014 | NM_000296 | c.11094C>G | EX38 | het | p.Y3698X | 0 | 0 | This study | Pathogenic | x |
K84 | Polycystic kidney disease | PKD2 | chr4:88964539 | NM_000297 | c.1249C>T | EX5 | het | p.R417X | 0 | 0 | [11] | Pathogenic | x |
K94 | Polycystic kidney disease | PKD1 | chr16:2160152 | NM_000296 | c.5014_5015del | EX15 | het | p.R1672fs | − 1 | 0 | [18] | Pathogenic | x |
PKD1 | chr16:2150245 | NM_000296 | c.9634T>G | EX28 | het | p.F3212V | 0.000008621 | 0.0000121 | This study | Uncertain significance | |||
PKD1 | chr16:2150244 | NM_000296 | c.9635T>C | EX28 | het | p.F3212S | 0.000008628 | 0.0000121 | This study | Uncertain significance | |||
K104 | Polycystic kidney disease | PKD1 | chr16:2154549 | NM_001009944:exon22: | c.8111C>T | EX22 | het | p.A2704V | 0.003471 | 0.00142 | [13] | Benign | |
K125 | Polycystic kidney disease | None | |||||||||||
K134 | Polycystic kidney disease | PKD1 | chr16:2140596 | NM_000296 | c.12136-5C>T | IVS44 | het | spl | 0.0006577 | 0.000545 | This study | Likely benign | |
K1 | Polycystic kidney disease | OFD1 | chrX:13757135 | NM_003611 | c.397_400delAAAG | hem | E134Ifs*10 | 0 | 0 | [19] | Pathogenic | x | |
K114 | Polycystic kidney disease | PKHD1 | chr6: 51712716 | NM_138694 | c.7964A>G | het | p.H2655R | 0 | 0 | This study | Uncertain significance | x | |
PKHD1 | chr6: 51935203 | NM_138694 | C.707+1G>A | het | spl | This study | Pathogenic | ||||||
K101 | multicystic kidney (CAKUT) | MUC1 | chr1:155159959 | NM_001204295 | c.309_316del | het | p.V103fs | − 1 | 0 | This study | Pathogenic | x |
Sample | Gender | Clinical diagnosis | Gene | Genomic position | Genetic sequence | cDNA change | ZYG | Protein change | ExAC | gnomAD | Reference | AMCG classification | Controls | Solved cases |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
K21 | F | Bardet-Biedl syndrome | BBS12 | chr4:123664149 | NM_152618 | C1102T | het | p.R368C | 0.00 | 0.00 | This study | Uncertain significance | x | |
K26 | M | Bardet-Biedl syndrome | BBS9 | chr7:33185869 | NM_198428 | c.6_6delT | het | p.L3Yfs*38 | 0.00 | 0.00 | This study | Pathogenic | x | x |
BBS9 | chr7:33384190 | NM_198428 | c.1276-2_1277delAGCA | het | Q426Sfs*5 | 0.00 | 0.00 | This study | Pathogenic | |||||
K29 | M | Bardet-Biedl syndrome | BBS2 | chr16:56531713 | NM_031885 | c.T1739G | het | p.L580R | 0.00 | 0.00 | This study | Uncertain significance | x | |
K30 | F | Bardet-Biedl syndrome | BBS4 | chr15:73007744 | NM_033028 | c.332+1G>GTT | hom | Spl? | 0.00 | 0.00 | This study | x | ||
K32 | F | Bardet-Biedl syndrome | BBS4 | chr15:73007744 | NM_033028 | c.332+1G>GTT | hom | spl? | 0.00 | 0.00 | This study | x | ||
K40 | F | Bardet-Biedl syndrome | TTC8 | chr14:89338776 | NM_001288782 | c.C733T | het | p.R245W | 0.00 | 0.00 | This study | Uncertain significance | ||
K41 | M | Bardet-Biedl syndrome | BBS12 | chr4:123665070 | NM_152618 | c.C2023T | hom | p.R675X | 0.00 | 0.00 | [20] | Pathogenic | x | x |
K45 | M | Bardet-Biedl syndrome | BBS10 | chr12:76741493 | NM_024685 | c.272_273insT | hom | p.C91Lfs*5 | 0.00 | 0.00 | This study | Pathogenic | x | |
K46 | M | Bardet-Biedl syndrome | BBS12 | chr4:123665070 | NM_152618 | c.C2023T | hom | p.R675X | 0.00 | 0.00 | [20] | Pathogenic | x | |
K49 | F | Bardet-Biedl syndrome | BBS4 | chr15:73007744 | NM_033028 | c.332+1G>GTT | hom | spl? | 0.00 | 0.00 | This study | x | ||
K50 | M | Bardet-Biedl syndrome | BBS2 | chr16:56533706 | NM_031885 | c.C1511T | het | p.A504V | 0.01 | 0.00 | [21] | Benign | x | |
K58 | F | Bardet-Biedl syndrome | BBS10 | chr16:2159557 | NM_024685 | c.641T>A | hom | p.V214E | 0.00 | 0.00 | This study | Uncertain significance | x | x |
K59 | F | Bardet-Biedl syndrome | None | |||||||||||
K69 | M | Bardet-Biedl syndrome | None | |||||||||||
K73 | F | Bardet-Biedl syndrome | BBS9 | chr7:33296990 | NM_ | c.585_586del | het | p.V196LFs*10 | 0.00 | 0.00 | This study | Pathogenic | x | |
chr7:33545112 | NM_ | c.2033delG | het | p.G678Afs*10 | 0.00 | 0.00 | This study | Pathogenic | ||||||
K88 | F | CARRIER(K73 mother) | BBS9 | chr7:33296990 | NM_ | c.585_586del | het | p.V196LFs*10 | 0.00 | 0.00 | This study | Pathogenic | ||
K89 | M | carrier(k73 father) | BBS9 | chr7:33545112 | NM_ | c.2033delG | het | p.G678Afs*10 | 0.00 | 0.00 | This study | Pathogenic | ||
K74 | M | Bardet-Biedl syndrome | BBS4 | chr15:73007744 | NM_033028 | c.332+1G>GTT | het | spl | This study | x | ||||
BBS4 | chr15:73027508 | NM_033028 | c.1091C>A | het | p.A364E | 0.00 | 0.00 | [22] | Likely pathogenic | |||||
K77 | F | Bardet-Biedl syndrome | BBS9 | chr7: 33312706 | NM_001348042 | c.T785C | hom | p.V262A | 0.00 | 0.00 | [23] | Likely pathogenic | x | |
K83 | M | Bardet-Biedl syndrome | None | |||||||||||
K87 | F | Bardet-Biedl syndrome | BBS9 | chr7:33380537 | NM_001033604 | c.T1227A | het | p.D409E | 0.00 | 0.00 | This study | Uncertain significance | ||
BBS4 | chr15:73009119 | NM_033028 | c.334_338del | het | p.112_113del | 0.00 | 0.00 | This study | Pathogenic | |||||
K105 | Bardet-Biedl syndrome | BBS12 | chr4:123663945 | NM_152618 | c.898C>T | hom | p.Q300X | 0.00 | 0.00 | This study | Pathogenic | x | ||
K107 | Bardet-Biedl syndrome | None | ||||||||||||
K115 | Bardet-Biedl syndrome | None | ||||||||||||
K116 | Bardet-Biedl syndrome | BBS10 | chr12:76741234 | NM_024685 | c.531C>A | het | p.Y177X | 0.00 | 0.00 | This study | Pathogenic | x | ||
BBS10 | chr12:76741492 | NM_024685 | c.273C>G | het | p.C91W | 0.00 | 0.00 | [24] | Pathogenic | |||||
K124 | M | Bardet-Biedl syndrome | None | |||||||||||
K128 | Bardet-Biedl syndrome | None | ||||||||||||
K131 | Bardet-Biedl Syndrome | BBS9 | chr7:33195293 | NM_001348042 | c.175del | het | p.C59fs*20 | 0.00 | 0.00 | This study | Pathogenic | x | ||
BBS9 | chr7:33384190 | NM_001348042 | C.1141_1142del | het | p.Q381Sfs*5 | 0.00 | 0.00 | This study | Pathogenic | |||||
K132 | Bardet-Biedl syndrome | bbs4 | chr15:73007744 | NM_033028 | c.332+1G>GTT | het | Spl? | This study | ||||||
K75 | M | Alport syndrome | no mut | |||||||||||
K85 | M | Alport syndrome | COL4A5 | chrX:107816858 | NM_000495 | c.520G>C | hem | p.G174R | 0.00 | 0.00 | [25] | Pathogenic | x | |
K95 | Alport Syndrome | None | ||||||||||||
K96 | Alport Syndrome | None | ||||||||||||
K100 | Alport Syndrome | COL4A5 | chrX:107816858 | NM_000495 | c.520G>C | het | p.G174R | 0.00 | 0.00 | [25] | Pathogenic | x | ||
K109 | Alport Syndrome | COL4A3 | chr2:228159682 | NM_000091 | c.3421C>A | het | p.L1141I | − 1.00 | 0.00 | This study | Uncertain significance | |||
COL4A3 | chr2:228159677 | NM_000091 | c.3419-3C>A | het | spl | − 1.00 | 0.00 | This study | Uncertain significance | |||||
COL4A3 | chr2:228172415 | NM_000091 | c.4253-11G>C | het | spl | 0.00 | 0.00 | This study | Uncertain significance | |||||
K110 | Alport Syndrome | COL4A5 | chrX:107816858 | NM_000495 | c.520G>C | het | p.G174R | 0.00 | 0.00 | [25] | Pathogenic | x | ||
K99 | Alport Syndrome | COL4A5 | chrX:107816858 | NM_000495 | c.520G>C | het | p.G174R | 0.00 | 0.00 | [25] | Pathogenic | x | ||
K121 | Alport Syndrome | COL4A5 | chrX:107868947 | NM_000495.5 | c.3032deIC | het | p.P1011Lfs*10 | 0.00 | 0.00 | This study | Pathogenic | x | ||
K122 | Alport Syndrome | COL4A5 | chrX:107868947 | NM_000495.5 | c.3032deIC | het | p.P1011Lfs*10 | 0.00 | 0.00 | This study | Pathogenic | x | ||
K42 | F | Alport syndrome | COL4A4 | chr2:227920747 | NM_000092 | c.G2630A | het | p.R877Q | 0.00 | 0.00 | [26] | Benign | x | |
COL4A4 | chr2:227973562 | NM_000092 | c.680G>A | het | p.R227H | 0.00 | 0.00 | This study | Uncertain significance | |||||
K3 | M | Tubulopahty (fanconi) | SLC2A2 | chr3:170720364 | NM_001278658.2 | c.711+1G>A | het | p.R182X | 0.00 | 0.00 | This study | Pathogenic | x | |
K16 | F | Tubulopathy (hypokalemic metabolic acidosis) | None | |||||||||||
K22 | Carrier (K16 mother) | |||||||||||||
K17 | F | Tubulopathy (hypokalemic metabolic acidosis) | SLC12A3 | chr16:56938322 | NM_000339 | c.2899A>G | hom | p.R967G | 0.00 | 0.00 | This study | Likely pathogenic | x | |
K18 | F | Tubulopathy (hypokalemic metabolic acidosis) | SLC12A3 | chr16:56933468 | NM_000339 | c.2687G>A | het | p.R896Q | 0.00 | 0.00 | [27] | Likely pathogenic | x | |
SLC12A3 | chr16:56933491 | NM_000339 | c.2710A>T | het | p.I904F | 0.00 | 0.00 | This study | Uncertain significance | |||||
K19 | F | Tubulopathy (hypokalemic metabolic acidosis) | SLC12A3 | chr16:56933468 | NM_000339 | G2687A | het | p.R896Q | 0.00 | 0.00 | [27] | Likely pathogenic | x | |
SLC12A3 | chr16:56933491 | NM_000339 | c.2710A>T | het | p.I904F | 0.00 | 0.00 | This study | Uncertain significance | |||||
K36 | F | Tubulopathy (hypokalemic metabolic alkalosis | None | |||||||||||
K39 | F | Tubulopathy (hypokalemic metabolic acidosis) | SLC12A3 | chr16:56916409 | NM_000339 | c.1669G>C | het | p.G557R | 0.00 | 0.00 | This study | Likely pathogenic | x | |
SLC12A3 | chr16:56921879 | NM_000339 | c.2221G>A | het | p.G741R | 0.00 | 0.00 | [28] | Likely pathogenic | |||||
K47 | F | Tubulopathy (hypokalemic metabolic alkalosis | None | |||||||||||
K65 | F | Tubulopathy (hypokalemic metabolic alkalosis | None | |||||||||||
K78 | M | Tubulopathy (hypokalemic metabolic alkalosis | None | |||||||||||
K103 | Tubulopathy/hypokalemic metabolic alkalosis) | CLCNKB | chr1:16378205 | NM_000085 | c.1298G>A | hom | p.G433E | 0.00 | 0.00 | [29] | Likely pathogenic | x | ||
K106 | Tubulopathy/hypokalemic metabolic alkalosis) | None | ||||||||||||
SLC12A3 | chr16:56913006 | NM_000339 | c.1202C>T | het | p.A401V | − 1.00 | 0.00 | This study | Uncertain significance | |||||
K117 | Tubulopathy/hypokalemic metabolic alkalosis) | CLCNKB | chr1:16374487 | NM_000085 | c.446T>A | hom | p.V149E | 0.00 | 0.00 | [30] | Likely pathogenic | x | ||
K2 | F | CAKUT | None | |||||||||||
K35 | M | CAKUT | None | |||||||||||
K98 | CAKUT | None | ||||||||||||
K61 | F | CAKUT | None | |||||||||||
K63 | M | CAKUT | None | |||||||||||
K52 | F | Tubulopahty (Renal Glucosuria) | SLC5A2 | chr16:31499413 | NM_003041 | c.940T>C | het | p.C314R | 0.00 | 0.00 | This study | Uncertain significance | ||
SLC5A2 | chr16:31500293 | NM_003041 | c.1373C>A | het | p.A458E | 0.00 | 0.00 | This study | Uncertain significance | |||||
K86 | F | Tubulopathy (Renal Glucosuria) | None | |||||||||||
K68 | F | Tubulopathy (Renal Glucosuria) | SLC5A2 | chr16:31499413 | NM_003041 | c.940T>C | het | p.C314R | 0.00 | 0.00 | This study | Uncertain significance | ||
K43 | M | Tubulopahty (Hypercalciuria) | None | |||||||||||
K53 | F | Tubulopathy (hypercalciuria) | SLC34A1 | chr5:176812822 | NM_001167579 | c.80C>T | het | p.T27M | 0.00 | 0.00 | This study | Uncertain significance | ||
EHHADH | chr3:184910069 | NM_001166415 | c.1829A>T | het | p.N610I | 0.00 | 0.00 | Benign | Benign | |||||
K27 | F | Tubulopahty (Hypercalciuria) | None | |||||||||||
K97 | Tubulopathy (hypercalciuria) | |||||||||||||
K7 | F | Tubulopathy (hypercalciuria) | None | |||||||||||
K8 | M | Tubulopathy (hypercalciuria) | None | |||||||||||
K120 | Tubulopathy (hypercacliuria) | None | ||||||||||||
K133 | F | Tubulopathy (hypercacliuria) | None | |||||||||||
K11 | F | Tubulopathy (RTA) | None | |||||||||||
K102 | Tubulopathy (RTA) | ATP6V0A4 | chr7:138434066 | NM_020632 | c.1030-6T>- | het | spl | − 1.00 | This study | Uncertain significance | ||||
K123 | Tubulopathy (cystinuria) | SLC7A9 | chr19:33355167 | NM_001126335 | c.313G>A | het | p.G105R | 0.00 | 0.00 | [30] | Pathogenic | x | ||
SLC7A9 | chr19:33324187 | NM_001126335 | c.1266_1267del | het | p.L424Gfs*63 | 0.00 | 0.00 | This study | Pathogenic | |||||
K12 | M | Tubulopathy (Diabetes Insipidus) | AVPR2 | chrX:153171298 | NM_000054 | c.338G>A | hem | p.R113Q | 0.00 | 0.00 | This study | Likely pathogenic | x | |
K20 | M | Tubulopathy (hypertension) | None |