Table 3.

Information on identified candidate mutations in congenital anomalies of the kidney and urinary tract genes known to cause isolated or syndromic congenital anomalies of the kidney and urinary tract

IdentificationaGeneMode of TransmissionNucleotide ChangeAmino Acid ChangeStateEvolutionary ConservationbPP2 SIFT MTCADD ScoreEVScgnomADcACMGdHGMDePhenotypesSegregation
A387KAT6BfDominantc.2152C>Tp.Arg 718TrpHetSaccharomyces cerevisiaeg0.983 Del. D.C.16//Uncertain significanceGeneL RA, R hydronephrosis; progressive renal impairmentVariant inherited from father (affection status unknown)
A870NOTCH2fDominantc.3556T>Ap.Tyr 1186AsnHetDanio rerio0.854 Del. D.C.180/1/42990/12/277048Uncertain significanceGeneBL VUR nevus pigmentosus R supranummery nippleVariant inherited from mother (affection status unknown)
A3401NOTCH2fDominantc.6767G>Ap.Arg 2256HisHetCiona intestinalish0.862 Del. D.C.150/1/42990/12/246058Uncertain significanceGeneR RHD, L UVJOVariant inherited from father (affection status unknown); segregates in two affected siblings
B17KMT2DfDominantc.13190G>Tp.Gly 4397ValHetDrosphilia melanogaster0.960 Del. D.C.11//Uncertain significanceGeneL RANA
A3095NSDHLfX-linked recessivec. 842G>Ap.Arg 281HisHemiX. tropicalis0.899 Del. D.C.12/0/6/8/199924Uncertain significanceGenePrune belly syndromeNA
A5063EP300fDominantc.1781C>Tp.Thr594MetHetD. melanogasteri0.999 Del. D.C.32/0/17/246260Uncertain significanceGeneBL MCDKVariant inherited from father (affection status unknown); segregates in two affected siblings
B258TP63fDominantc.799G>Ap.Val267IleHetC. intestinalisj0.802 Tol. D.C.22/0/3/246070Uncertain significanceGeneL UPJONA
A3957NOTCH2fDominantc.6892C>Tp.Arg2298TrpHetD. rerio0.609 Del. D.C.11/0/1/245696Uncertain significanceGeneBL hydronephrosisNA
Anorectal malformation
A3960FGFR1fDominantc.1426C>Tp.Arg476TrpHetD. rerio1.000 Del. D.C.6/0/4/277084Uncertain significanceGeneL RA, R VURNA
Bladder extrophy
B1307AMER1fDominantc.185G>Tp.Gly62ValHetD. rerio0.813 Tol. D.C.190/1/1/24270/4/9/200427Uncertain significanceGeneR MCDKNA
B1398kOFD1fX-linkedc.936–2A>G100% ESSHet/NA0/0/1/24270/8/23/198443Uncertain significanceGeneBL VURVariant inherited from mother (affection status unknown)
R hydronephrosis
B1440HOXA13fDominantc.25C>Tp.Pro9SerHetD. rerio0.992 Tol. D.C.18/0/28/226114Uncertain significanceGeneBL hydronephrosisNA
Facial dysmorphism
A2904FGFR3fDominantc.1663G>Ap.Val555MetHetD. melanogaster0.985 Del. D.C.19/0/48/274072Likely pathogenicDMR RHD, VURNA
B120OFD1fDominantc.517+1G>A100% ESSHet/NA//PathogenicGeneR MCDKNA
L duplex
L VUR, ureterocoele
B1652kFLNAfX-linked recessivec.6348C>Gp.His2116GlnHemiCaenorhabditis elegans0.955 Del. D.C.12//Uncertain significanceGenePrune belly syndromeVariant inherited from mother (affection status unknown)
Neurogenic bladder
  • PP2, PolyPhen 2; SIFT, Sorting Intolerant from Tolerant; MT, Mutation Taster; CADD, Combined Annotation Dependent Depletion; EVS, Exome Variant Server; gnomAD, Genome Aggregation Database; ACMG, American College of Medical Genetics; Het, heterozygous; Del., deleterious; D.C., disease causing; /, data not available; L, left; RA, renal agenesis; R, right; BL, bilateral; VUR, vesicoureteric reflux; RHD, renal/hypodysplasia; UVJO, ureterovesical junction obstruction; PUV, posterior urethral valve; NA, not available; Hemi, hemizygous; MCDK, multicystic dysplastic kidney; Tol., tolerated; UPJO, ureteropelvic junction obstruction; —, not applicable; ESS, essential splice site; DM, disease mutation.

  • a Unique family identification number.

  • b Evolutionary conservation was assessed across phylogeny over eight species: Mus musculus, Gallus gallus, Xenopus tropicalis, Danio rerio, Caenorhabditis elegans, Ciona intestinalis, Drosphilia melanogaster, and Saccharomyces cerevisiae. If conservation is interrupted in one species but otherwise preserved across phylogeny, additional information is outlined.

  • c Variant frequencies listed for homozygous/hemi (if applicable)/het/total alleles detected in the population.

  • d ACMG American College of Human Genetics Standards and Guidelines Classification as pathogenic, likely pathogenic, or uncertain significance.66

  • e HGMD Human Gene Mutation Database; ( If the exact variant has previously been reported and classified as a pathogenic mutation that is disease causing, the variant is denoted as DM. If the gene but not the exact variant has been reported for the corresponding phenotype, gene is indicated.

  • f Mutations in syndromic genes identified in families with an isolated syndromic congenital anomaly of the kidney and urinary tract phenotype.

  • g Interruption in conservation due to glutamine present in D. rerio and D. melanogaster.

  • h Interruption in conservation due to leucine present in D. rerio.

  • i Interruption in conservation due to glutamate present in C. elegans.

  • j Interruption in conservation due to asparagine present in X. tropicalis.

  • k Finding in more than two categories.