Table 2.

Demographics, genetic information, and effect on management for patients with diagnostic genetic results

Patient NumberSexAge(yr)L1L2L3L4L5Type of Genetic Testing (1, 2, 3, 4, 5)aGene/LocusGenetic Finding (SNV/Indel/CNV)Phenotype (Indication for Referral)Comment
RGC-0001F10++1PKD1NM_001009944.2: c.7987C>T (p.Q2663*) (het)Bilateral renal cysts
RGC-0003M0.8+++4PKD1Partial PKD1 gene deletion (at least exons 27–38) (het) (novel)Bilateral renal cystsSubsequently mother was found have cysts in her kidneys
RGC-0004M13+++2HNF1Barr[GRCh37]2q36.3 (227999132_228097605)x1Chromosomal abnormalityDeletion was found to be maternally inherited
RGC-0009M10+++1PKD1NM_001009944.2: c.7483T>C (p.C2495R) (het)Bilateral renal cysts and duplicated collecting systemSymptomatic sibling tested positive for KFM
RGC-0010M16++1COL4A5NM_000495.4: c.152G>T (p.G51V) (hem)Hematuria and proteinuriaSymptomatic sibling tested positive for KFM
RGC-0013M3+1COL4A5NM_000495.4: c.3197G>C (p.G1066A) (hem)Alport syndrome
RGC-0014F10++21q21 delarr[GRCh37]1q21.1q21.2 (146618988–147825855)x1Learning disability, VUR, cataracts, microcephalyPatient also has 16p11.2 0.521 Mb duplication
RGC-0018M1.5++2HNF1Barr[GRCh37] 17q12 (34842059–36214026)x1Unilateral multicystic dysplastic kidney, VUR, hypercalcemia, developmental delay, hypotonia
RGC-0019F16+2, 3WDR19NM_025132: c.3703G>A (p.E1235K) (het) arr[GRCh37]4p14 (39215680–39219295)x1ESKD, dysautonomia, migraines, choledochal and pancreas cyst
RGC-0021F2.7+++2, 4PKD1NM_001009944.2: c.1259A>G (p.Y420C) (het)Cystic kidney and Chiari malformationPKD1 variant is de novo
RGC-0026F4++2, 4EYA1arr[GRCh37]8q13.2q13.3 (69901440–72586292)x1Branchio-oto-renal syndromeEYA1 variant is de novo
RGC-0029M2.9++1PKD1NM_001009944.2: c.2659delT (p.W887Gfs*11) (het)Bilateral renal cysts
RGC-0030F1.5+++1NPHS2NM_014625: c.790G>C (p.E264Q) (het), and c.779T>A (p.V260E) (het)Infantile nephrotic syndromePhase of the variants were determined (opposite chromosomes), subsequently symptomatic siblings tested positive for these variants
RGC-0032M12++2, 4DYRK1ANM_001396: c. 501delA (p.G168fs) (het)Intellectual disability and hypospadiasDYRK1A variant is de novo
RGC-0034F2.6++++1, 2, 4WT1NM_024426.4: c.1390G>A (p.D464N) (het)Atypical HUSWT1 variant is de novo
RGC-0039F7+++2, 4COL4A3NM_000091: c.1407delA (p.G470fs) (het) and c.40_63del (p.L14_L21del) (het)Hereditary nephritisEach variant is inherited from one parent
RGC-0041M15++222q11 triplicationarr[GRCh37]22q11.1q11.21 (17289827–18640328)x3Facial asymmetry, imperforate anus, neurogenic bladderThis triplication is de novo
RGC-0043M11++2, 4KAT6BNM_012330: c.3280delG (p.E1094fs) (het)Bilateral undescended testes, a mild hypospadias, and Ohdo syndromeKAT6B variant is de novo
RGC-0046M3++1NPHS2NM_014625: c.790G>C (p.E264Q) (het), and c.779T>A (p.V260E) (het)Positive family history of infantile nephrotic syndromeAvoid immune suppression
RGC-0047F2++1NPHS2NM_014625: c.790G>C (p.E264Q) (het) and c.779T>A (p.V260E) (het)Infantile nephrotic syndromeAvoid immune suppression
RGC-0050M18++2, 4TMEM67NM_153704: c. 515G>T (p.R172L) (het) and c.1021G>A (p.G341R) (het) (novel)Joubert syndromeEach variant is inherited from one parent
RGC-0052M0.8+++2, 4NSD1NM_022455.4: c.3423_3424insCC (p.N1142PfsX11) (het) (novel)Macrosomia and nephromegalyNSD1 variant is de novo
RGC-0054M1.9+++2, 4PLCE1NM_016341.3: c.4675_4678delITTAG (p.L1559fs) (hom) (novel)Nephrotic-range proteinuriaEach variant is inherited from one parent
RGC-0055M10++1PKD1NM_001009944.2: c.7483T>C (p.C2495R) (het)Family history of ADPKD, bilateral cystic kidney disease, and duplicated collecting system
RGC-0058M3+1ATP6V0A4NM_020632.2: c.1231G>T (p.D411Y) (hom)Distal renal tubular acidosisHearing evaluation was normal
RGC-0063F3+1PKD1NM_001009944.2: c.7111del (p.V2371Cfs*11) (het)Bilateral renal cystsEchocardiogram
RGC-0066F19+++2, 4USP9XNM_001039590.2: c.5606_5607dupTC (p.V1870SfsX37) (het) (novel)Hypertension and Townes–Brocks syndromeUSP9X variant is de novo
RGC-0067M4.9+++2, 4COL4A5NM_000495: c.5034T>A (p.C1678X) (hem) (novel)Hematuria and thin basement membrane nephropathyCOL4A5 variant is maternally inherited
RGC-0068M14+++2, 4OCRLNM_000276.3: c.2531_2539delGAGAACTC TinsAAG (p.R844_L847delinsQV) (hem) (novel)Cataracts and proteinuriaOCRL variant is maternally inherited, subsequently sibling tested positive for KFM
RGC-0070F13++2, 3NPHP4NM_015102.3: c.3611C>T (p.P1204L) (hom)CKD
RGC-0072M11++2, 3PKD1NM_001009944: c.9859_9861del (p.L3287del) (het)Bilateral renal cysts
RGC-0075F14++2, 3DCDC2NM_016356: c.383C>G (p.S128X) (hom)ESKD and liver fibrosis
RGC-0076M4++1COL4A5NM_000495.4: c.1948G>A (p.G650S) (hem)Alport syndromeSiblings tested negative for KFM
RGC-0077F6+++1PKD1NM_001009944.2: likely pathogenic c.8948+1G>T (het), VUS c.955GG>C (p.Vl3184L) (het)Bilateral renal cystsEach variant in PKD1 is inherited from one parent
RGC-0078F1.9+++1PKD1Likely pathogenic c.9829C>T (p.R3277C) (het), VUS c.3494A>G (p. D1165G) (het)Bilateral renal cystsEach variant in PKD1 is inherited from one parent
RGC-0080M12+++1PKHD1NM_138694.3: likely pathogenic (c.3761_3762delinsG) (p.A1254Gfs*49) (het), VUS c.4292G>A (p.C1431Y) (het)Bilateral renal cystsPseudodominant ARPKD, each variant is inherited form one parent; both father and paternal aunt are clinically diagnosed with ARPKD
RGC-0081M13++2, 4COL4A5arr[GRCh37]Xq22.3 (107802035–107802303)x0 (Novel)Alport syndrome, developmental delay, autism, ADHDThis deletion is maternally inherited
RGC-0083M16++++2, 4COL4A5NM_000495: c.3059dupT (p.G1021fs) (hem) (novel)FSGSBoth patient and his affected mother’s diagnosis has been changed and avoid immune suppression
RGC-0084F4.9+++2, 4RMND1NM_017909: c.713A>G (p.N238S) (het) and c.533C>T (p.T178M) (het)CKD, congenital hearing loss, and developmental delayEach variant is inherited from one parent
RGC-0085M0.5++2, 4CASKNM_003688: c.1721dupA (p.S575fs) (hem) (novel)Microcephaly, dysmorphic features, right club feet, neurologic dysfunction, hypotonia, pontocerebellar hypoplasia, and right cryptorchidismVariant in CASK is de novo
RGC-0086M0.2++21q23.2q25.1 deletionarr[GRCh37]1q23.2q25.1 (160369890–175796325)x1Multiple congenital anomalies including dysplastic ears, dysplastic kidney, bilateral undescended testes, dysmorphic features, and abnormality of the shape of hands
RGC-0087M9+++1PKD1NM_001009944.2: c.11017–10C>A (IVS37–10C>A) (het)Bilateral renal cystsPKD1 variant is inherited from father; subsequently, father and PGF were diagnosed with ADPKD
RGC-0088F6+1PKD1NM_001009944.2: c.6806C>G (p.S2269*) (het)Bilateral renal cysts
RGC-0090F18+1COL4A5NM_000495.4: c.4602del (p.Y1535Ifs*13) (het) (novel)Alport syndrome
RGC-0091M8++2, 3PKD1NM_001009944.2: c.8043_8046delCTCG (p.S2682Afs*2) (het) (novel)Bilateral renal cysts
RGC-0092F2++2, 4PKHD1NM_138694.3: pathogenic variant c.3761_3762delCCinsG (het), VUS c.10666C>T (p.R3558C) (het)Bilateral renal cystsOne variant is inherited from one parent and the other one is de novo
RGC-0097F17+++4COL4A5NM_033380.1: c.3631G>A (p.G1211R) (het)Hereditary nephritisCOL4A5 variant is de novo
RGC-0100M15++1HNF1BNM_000458.2: c.513G>A (p.W171X) (het)Bilateral renal cysts
RGC-0101M16+1COL4A5arr[GRCh37]Xq22.3 (107868501–107869156)x0 (novel)Alport syndrome
RGC-0105F8++1COL4A4NM_000092.4: c.1334G>C (p.G445A) (het) and c.2570C>T (p.P857L) (het)Steroid-sensitive nephrotic syndrome
RGC-0108M15+++1, 4OCRLNM_000276.3: c.239delG (p.S80MfsX26) (hem) (novel)ProteinuriaOCRL variant was maternally inherited
RGC-0110M5+++5WDR19NM_025132: pathogenic c.1122_1123insT (p.P375fs) (het) (novel) and VUS c.817A>G (p.N273D) (het)ESKDEach variant in WDR19 is inherited from one parent
RGC-0112M14++2NPHP1arr[GRCh37]2q13 (110862477–110970270)x1CKD
RGC-0113F6+++2, 4PKD2NM_000297.3: c. 965G>A (p.R322Q) (het)VUR, duplicated collecting system, and bilateral cystic kidneyPKD2 variant is paternally inherited
RGC-0115F7++1PKD2NM_000297.3: c.2614C>T (p.R872*) (het)Unilateral renal cysts
RGC-0116F1+++1, 2, 5RPS19NM_001022: c.185G>A (p.R62Q) (het)CKD and Diamond–Blackfan anemiaRPS19 variant is de novo
RGC-0117M0.16+++2, 4BBS12NM_152618.2: pathogenic c.1115_1116delTT (p.F372*) (het), and VUS c.1277G>A (p.C426Y) (het)Polydactyly and bilateral renal cystsEach variant in BBS12 is inherited from one parent
RGC-0118M9++++2, 4KCNJ1NM_000220.3: c.924C>A (p.C308*) (hom)Renal dysplasiaBoth parents are heterozygous for variant in KCNJ1
RGC-0120M17++2, 4INVSNM_014425.3: c.2695C>T (p.R899*) (hom)NephronophthisisBoth parents are heterozygous for variant in INVS
RGC-0124F17+1COL4A4NM_000092.4: c.1580del, (p.G527Vfs*126) (het)Microscopic hematuria
RGC-0128M2+1PKD1NM_01009944.2: c.8016+2T>C (IVS21+2T>C) (het)Bilateral renal cysts
RGC-0129M14+2, 4SLC7A9NM_014270.4: c.419T>C (p.F140S) (het) and c.164T>A (p.V55E) (het) (novel)Cystine stones and dysplastic kidneyEach variant in SLC7A9 is inherited from one parent
RGC-0132F17++1PKD1NM_001009944.2: c.11712+1G>A (het)Bilateral renal cysts
RGC-0143M2+++1NPHS1NM_004646.3; c.1747G>A (p.S910P) (het) (likely pathogenic), and c.1747G>A (p.E583K) (het) (VUS)Nephrotic syndromeAvoid immune suppression
RGC-0145M16++1NEK8NM_178170.2: c.1523T>A (p.Met508Lys) (het), and c.673G>C (p.Asp225His) (het)Cystic kidney diseaseClinical diagnosis of ARPKD was changed to nephronophthisis
RGC-0147M14++2, 4KCNJ1NM_000220.3: c.924C>A, (p.C308*) (hom)Bartter syndromeBoth parents are heterozygous for variant in KCNJ1
RGC-0152F10++1COL4A5NM_000495.4: c.994_998delinsTCCC (p.Q332Sfs*14) (het) (novel)Alport syndrome
RGC-0156M14+++1COL4A5NM_000495.4: c.4688+1G>T (hem)Alport syndromeCOL4A5 variant is maternally inherited and sibling was tested negative for KFM
RGC-0157M12++1COL4A4NM_000092.4; c.1325G>C (p.G442A) (het)Microscopic hematuria
RGC-0159M2+1COL4A4NM_000092.4: c.1697–1G>A (het)Microscopic hematuria
RGC-0160M5++1AVPR2NM_000054.4: c.337C>T (p.R113W) (hem)Diabetes insipidusSubsequently sibling was tested positive for KFM
RGC-0162F8+1COL4A5NM_000495.4: c.2678G>A (p.G893D) (het)Microscopic hematuria
RGC-0164bM1.3+++4HNF1BArr[GRCh37]17q12 (34856055–36248918)x1dnBilateral renal cystsThis deletion is de novo and secondary finding of BRCA2 is maternally inherited
RGC-0171M2++++2, 4WT1NM_024426.4: c.1432+4C>T (het)Proteinuria, recurrent UTI, and hypospadiasWT1 variant was de novo
RGC-0182F11++1COL4A5NM_000495: c.557G>A (p.Gly186Asp) (het) (novel)Microscopic hematuriaFamilial diagnosis of FSGS changed to Alport syndrome
RGC-0183F16++1SLC12A3NM_000339; c.1001G>A (p.R334Q) (hom)Gitelman syndrome
RGC-0185F0.1++2, 5TPRM6NM_017662.4: c.5488–1G>C (hom) (novel)HypomagnesemiaHypocalcemia and hypomagnesemia are due to defect in intestinal absorption of magnesium
RGC-0186M0.9++1WT1NM_0024426.3: c.1288C>T (p.R430*) (het) (novel)Bilateral Wilms tumorImpacted nephrectomy
RGC-0190F10++++2, 4WT1NM_024426.4: c.1432+5 G>A (het)ESKD and nephrotic range proteinuriaCMA revealed patient is XY female, and WT1 variant is de novo
RGC-0191F11++1CACNA1SNM_000069.2: c.3715C>G (p.R1239G) (het)HypokalemiaTreatment with acetazolamide
RGC-0192M18+++1, 2, 4COL4A5NM_000495.4: c.4298–20T>A (hem) (novel)Hematuria and proteinuriaCOL4A5 variant is maternally inherited
  • L1, effect on medical and/or surgical treatment; L2, change of medical diagnosis; L3, providing diagnostic certainty; L4, subsequent evaluation of other body-system involvement; L5, cascade family member testing; SNV, single nucleotide variant; CNV, copy number variant; F, female; M, male; het, heterozygous; KFM, known familial mutation; hem, hemizygous; del, deletion; VUR, vesicoureteral reflux; HUS, hemolytic uremic syndrome; ins, insertion; hom, homozygous; ADPKD, autosomal dominant polycystic kidney disease; VUS, variant of uncertain significance; ARPKD, autosomal recessive polycystic kidney disease; ADHD, attention deficit hyperactivity disorder; PGF, paternal grandfather; UTI, urinary tract infection; CMA, chromosomal microarray.

  • a Numbers represent the following testing types: 1, panel; 2, CMA; 3, proband exome sequencing; 4, trio exome sequencing; 5, Total BluePrint.

  • b Patient had a secondray finding of pathogenic variant in BRCA2.