Table 4.

Variants in other genes reported in dominant forms of CAKUT, including previously reported variants and novel rare variants

Patient	Renal Phenotypea	Extrarenal Phenotype	Gene	NM_ref	Nucleotide Change	Amino Acid Change	No. of Missense Deleterious Scoresb	ExACc	Inheritance	Ref.	Other Variant(s)
Novel rare variants in individuals with CAKUT
K94	UKA+	Didelphys uterus	BICC1	001080512	c.[2264C>G];[=]	p.[Thr755Arg];[=]	4/5	0	NAd
K127	UKA+	No	BICC1	001080512	c.[1052G>A];[=],	p.[Cys351Tyr];[=]	3/5	0	Unaffected mother plus affected brothere		DSTYK, SOX17f
K160	UKA	Deafness plus branchial defect plus colobomatous microphtalmia	CDC5L	001253	c.[2240T>G];[=]	p.[Leu747Trp];[=]	4/5	0	Fatherg		CHD7 causative
K162	RH+	Palate cleft plus preauticular pit	CDC5L	001253	c.[251C>G];[=]	p.[Thr84Ser]; [=]	5/5	0	NAe
K70	BMD	No	CHD1L	004284	c.[1557A>C];[=],	p.[Lys519Asn];[=]	4/5	0	NAd		NOTCH2, SALL4
K127	UKA+	No	DSTYK	015375	c.[2674G>A];[=]	p.[Asp892Asn];[=]	3/5	0.0075% NFE	Unaffected mother plus affected brothere		BICC1, SOX17f
K32	RH	No	NOTCH2	024408	c.[1063G>A];[=]	p.[Asp355Asn];[=]	3/5	0.0015% NFE	NAd		RETf
K70	BMD	No	NOTCH2	024408	c.[5156G>A];[=]	p.[Arg1719Gln];[=]	3/5	0.012% EAS	NAd		CHD1L, SALL4
K190	RH+	No	NOTCH2	024408	c.[854G>A];[5903C>T]	p.[Arg285His]	4/5; 5/5	0.0087% AMR; 0	One from each parenth
K83	BMD	No	RET	020975	c.[2063C>T];[=]	p.[Ser688Phe];[=]	5/5	0	Unaffected fathere
K91	UKA	No	RET	020975	c.[1903C>T];[=]	p.[Arg635Cys];[=]	5/5	0.012% SAS	Unaffected mother plus affected brothere
K69	BMD	No	SALL1	002968	c.[3771C>G];[=]	p.[Asn1257Lys];[=]	4/5	0	NAd
K70	BMD	No	SALL4	020436	c.[2492G>A];[=]	p.[Arg831Gln];[=]	3/5	0	NAd		CHD1L, NOTCH2
K29	BKA	Small testis	SIX5	175875	c.[2189C>T];[=]	p.[Ser730Leu];[=]	4/5	0.012% NFE	NAd
K56	RD	Interventricular communication plus intrauterine growth retardation	TBC1D1	015173	c.[2790G>A];[=]	p.[Met930Ile];[=]	3/5	0	NAd
K105	RH+	No	TBC1D1	015173	c.[2152C>T];[=]	p.[Arg718Cys];[=]	4/5	0.015% FIN	NAd
K21	BMD	No	TBX18	001080508	c.[610C>T]; [=]	p.[His204Tyr];[=]	5/5	0.0015% NFE	NAd
K48	RH+	No	TBX18	001080508	c.[1483C>A];[=]	p.[Gln495Leu];[=]	5/5	0	Unaffected fatherd		GATA3 causative
K192	BKA	No	TBX18	001080508	c.[772A>G]; [=]	p.[Ile258Val];[=]	3/5	0	NAd
K169	UKA+	No	TNXB	019105	c.[563C>T]; [=]	p.[Pro188Leu];[=]	3/5	0g	NAd
Previously reported variantsf in individuals with CAKUT
K3	BKA	Right ventricular dilation	RET	020975	c.[1699G>A];[=]	p.[Asp567Asn];[=]	3/5	0.11% OTH	Unaffected father (absent in affected sister)e	13
K32	RH	No	RET	020975	c.[2081G>A];[=]	p.[Arg694Gln];[=]	2/5	0.049% SAS	NAd	18	NOTCH2
K127	UKA+	No	SOX17	022454	c.[775T>A]; [=]	p.[Tyr259Asn];[=]	2/5	1.75% OTH	Unaffected father plus affected brothere	19	BICC1, DSTYK
Previously reported variantsf in individuals with BO
BO11	No	Deafness	DSTYK	015375	c.[654+1G>A];[=]			0.088% AMR	NAd	20

UKA, unilateral kidney agenesis; NA, not available; RH, renal hypoplasia; BMD, bilateral multicystic dysplasia; NFE, non-Finnish European; EAS, East Asian; AMR, Latino; SAS, South Asian; BKA, bilateral kidney agenesis; RD, renal dysplasia; FIN, Finnish; OTH, Other populations.

^aPlus indicates presence of (a) secondary phenotype(s).

^bNumber of programs that predicted the variant as damaging among Polyphen2 (probably and possibly damaging), Sift (deleterious), MutationTaster (deleterious), Grantham (considered as deleterious when ≥50), and Grantham variation score and Grantham difference score (considered as deleterious when ≥C25).

^cOnly variant frequencies in the population with the higher level are indicated.

^dSporadic.

^eFamilial.

^fVariant reported in the literature with a frequency in the ExAC above the one to 5000 threshold.

^gClinical information not available.

^hMother affected with deafness without renal defect.