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Cystic kidney disease v8.5 IFT140 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype accessed 25th Feb 2026.
Cystic kidney disease v8.5 IFT140 Ida Ertmanska Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920; short-rib thoracic dysplasia 9 with or without polydactyly, MONDO:0009964; cystic kidney disease, MONDO:0002473 to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920; short-rib thoracic dysplasia 9 with or without polydactyly, MONDO:0009964; cystic kidney disease, MONDO:0002473; {Polycystic kidney disease 9, susceptibility to}, OMIM:621164
Cystic kidney disease v8.4 NEK8 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated on 25th Feb 2026.
Cystic kidney disease v8.4 NEK8 Ida Ertmanska Phenotypes for gene: NEK8 were changed from polycystic kidney disease, MONDO:0020642; ?Nephronophthisis 9, OMIM:613824 to Polycystic kidney disease 8, OMIM:620903; polycystic kidney disease, MONDO:0020642; ?Nephronophthisis 9, OMIM:613824
Cystic kidney disease v8.3 PKHD1 Arina Puzriakova Phenotypes for gene: PKHD1 were changed from Autosomal Recessive Polycystic Kidney Disease; Polycystic Kidney Disease, Autosomal Recessive; Polycystic kidney and hepatic disease, 263200 to Polycystic kidney disease 4 with or without hepatic disease, OMIM:263200
Cystic kidney disease v8.2 CYP24A1 Eleanor Williams Tag Q1_26_MOI tag was added to gene: CYP24A1.
Cystic kidney disease v8.2 CYP24A1 Eleanor Williams edited their review of gene: CYP24A1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v8.2 CYP24A1 Eleanor Williams changed review comment from: The OMIM entry for this gene disease association Hypercalcemia, infantile, 1, OMIM:143880 records an autosomal recessive mode of inheritance but no publications since 2011 have been assessed. There is now evidence that individuals may present with disease in adult hood, and some evidence that those with monoallelic variants present with milder disease.

Update on monallelic cases:

PMID: 21675912 - Schlingmann et al 2011 - report 7 families with homozgyous or compound heterozgyous variants in CYP24A1 and infantile hypercalcaemia and 1 case with a heterozygous deletion affecting a splice site but the authors note that there may be another undetected variant outside of the coding region. Analysis was of a few candidate genes only. Renal cysts were not assessed.

PMID: 22337913 - Tebben et al 2012 - proband (aged 44 years) with hypercalcemia and hypercalciuria and elevated serum 1,25(OH)2D. Only CYP24A1 and CYP27B were sequenced. 2 splice mutations in CYP24A1 were identified. Seven family members from three generations showed chemical and clinical phenotypes with one or two CYP24A1 mutations, suggesting autosomal dominant transmission with partial penetrance of the trait. Renal cysts were noted in the proband and one heterozygous child of the proband.

PMID: 24235083 - Colussi et al 2014 - report 2 unrelated probands with homozgyous variants in CYP24A1 and recurrent nephrolithiasis, chronic hypercalcaemia with depressed parathyroid hormone (PTH) and increased 1,25(OH)(2)D levels; heterozygous carriers had nephrolithiasis (two of six), hypercalciuria (two of six) and high or normal-high 1,25(OH)(2)D (four of four).  The authors conclude that heterozygous carriers may also have subtle abnormalities of vitamin D metabolism that predispose them to events such as renal stones.                                                                                                                                      

PMID: 26214117 - Molin et al 2015 - report 25 patients out of a pool of 72 with hypercalcemia that had CYP24A1 variants. Only this gene was screened. 20 had biallelic variants, mostly with nephrocalincosis or renal stones. 5 neonates were heterozygous without renal disease. Further investigation of relatives found a further 21 heterozygotes who were found to have normal serum calcium and PTH levels. They note that while most heterozygous individuals remain asymptomatic, hypercalcemia may occur due to excessive vitamin D intake.

PMID: 27129455 - O'Keeffe et al 2016 - ABSTRACT ONLY ACCESSED - report a family with affected individuals with both biallelic and monallelic variants in CYP24A1. A gene dose effect is apparent: subjects with biallelic, compound heterozygous mutations (A/B) have a more severe clinical and biochemical phenotype, whereas, subjects with monoallelic mutations demonstrate milder disease manifestations. However, they note that 2 subjects with monoallelic mutations had nephrolithiasis and one had non-PTH dependent hypercalcemia.

PMID: 34307984 - Hanna et al 2021 - report a high prevalance in of kidney cysts in patients with CYP24A1 deficiency. Looked at 16 patients from 12 pedigrees with confirmed pathogenic variants. Medullary and/or corticomedullary junction cysts were present in all cases. Heterozygous variants were reported in 2 families - patient 11, pedigree 7, and patients 1,2 and 3 in pedigree 1. Patient 10 was compound heterozygous. Family 1 is same family reported in Tebben et al 2012.

PMID: 38504242 - Wang et al 2024 - studied 6 patients with Idiopathic infantile hypercalcemia. 2 patients were found to have compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant (patient 1). Patient presented with hypercalcemia and had significant renal calcification.

PMID: 33249478 - Brancatella et al 2021 - ABSTRACT ONLY ACCESSED - a large family harboring the nonsense c.667A>T, p.Arg223* pathogenic variant in the CYP24A1 gene was evaluated. All subjects underwent clinical and biochemical evaluation and complete analysis of vitamin D metabolites. The 40 yo male proband proband, was homozygous for p.Arg223* pathogenic variant. Compared with the wild-types, heterozygotes had higher serum calcium and 25(OH)D3 concentrations, without any difference in the other biochemical parameters and in the rate of nephrolithiasis. The authors note that heterozygotes might require surveillance because of the potential risk of developing hypercalcemia and related clinical manifestations if exposed to triggering factors.

In conclusion, while the bulk of patients with Hypercalcemia have biallelic variants, those with monoallelic variants generally present with a milder phenotype, which may be amplified by exposure to high levels of vitamin D.; to: The OMIM entry for this gene disease association Hypercalcemia, infantile, 1, OMIM:143880 records an autosomal recessive mode of inheritance but no publications since 2011 have been assessed. There is now evidence that individuals may present with disease in adult hood, and some evidence that those with monoallelic variants present with milder disease.

Update on monoallelic cases where a phenotype is assessed:

PMID: 21675912 - Schlingmann et al 2011 - report 7 families with homozgyous or compound heterozgyous variants in CYP24A1 and infantile hypercalcaemia and 1 case with a heterozygous deletion affecting a splice site but the authors note that there may be another undetected variant outside of the coding region. Analysis was of a few candidate genes only. Renal cysts were not assessed.

PMID: 22337913 - Tebben et al 2012 - proband (aged 44 years) with hypercalcemia and hypercalciuria and elevated serum 1,25(OH)2D. Only CYP24A1 and CYP27B were sequenced. 2 splice mutations in CYP24A1 were identified. Seven family members from three generations showed chemical and clinical phenotypes with one or two CYP24A1 mutations, suggesting autosomal dominant transmission with partial penetrance of the trait. Renal cysts were noted in the proband and one heterozygous child of the proband.

PMID: 24235083 - Colussi et al 2014 - report 2 unrelated probands with homozgyous variants in CYP24A1 and recurrent nephrolithiasis, chronic hypercalcaemia with depressed parathyroid hormone (PTH) and increased 1,25(OH)(2)D levels; heterozygous carriers had nephrolithiasis (two of six), hypercalciuria (two of six) and high or normal-high 1,25(OH)(2)D (four of four).  The authors conclude that heterozygous carriers may also have subtle abnormalities of vitamin D metabolism that predispose them to events such as renal stones.                                                                                                                                      

PMID: 26214117 - Molin et al 2015 - report 25 patients out of a pool of 72 with hypercalcemia that had CYP24A1 variants. Only this gene was screened. 20 had biallelic variants, mostly with nephrocalincosis or renal stones. 5 neonates were heterozygous without renal disease. Further investigation of relatives found a further 21 heterozygotes who were found to have normal serum calcium and PTH levels. They note that while most heterozygous individuals remain asymptomatic, hypercalcemia may occur due to excessive vitamin D intake.

PMID: 27129455 - O'Keeffe et al 2016 - ABSTRACT ONLY ACCESSED - report a family with affected individuals with both biallelic and monallelic variants in CYP24A1. A gene dose effect is apparent: subjects with biallelic, compound heterozygous mutations (A/B) have a more severe clinical and biochemical phenotype, whereas, subjects with monoallelic mutations demonstrate milder disease manifestations. However, they note that 2 subjects with monoallelic mutations had nephrolithiasis and one had non-PTH dependent hypercalcemia.

PMID: 34307984 - Hanna et al 2021 - report a high prevalance in of kidney cysts in patients with CYP24A1 deficiency. Looked at 16 patients from 12 pedigrees with confirmed pathogenic variants. Medullary and/or corticomedullary junction cysts were present in all cases. Heterozygous variants were reported in 2 families - patient 11, pedigree 7, and patients 1,2 and 3 in pedigree 1. Patient 10 was compound heterozygous. Family 1 is same family reported in Tebben et al 2012.

PMID: 38504242 - Wang et al 2024 - studied 6 patients with Idiopathic infantile hypercalcemia. 2 patients were found to have compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant (patient 1). Patient presented with hypercalcemia and had significant renal calcification.

PMID: 33249478 - Brancatella et al 2021 - ABSTRACT ONLY ACCESSED - a large family harboring the nonsense c.667A>T, p.Arg223* pathogenic variant in the CYP24A1 gene was evaluated. All subjects underwent clinical and biochemical evaluation and complete analysis of vitamin D metabolites. The 40 yo male proband proband, was homozygous for p.Arg223* pathogenic variant. Compared with the wild-types, heterozygotes had higher serum calcium and 25(OH)D3 concentrations, without any difference in the other biochemical parameters and in the rate of nephrolithiasis. The authors note that heterozygotes might require surveillance because of the potential risk of developing hypercalcemia and related clinical manifestations if exposed to triggering factors.

In conclusion, while the bulk of patients with Hypercalcemia have biallelic variants, those with monoallelic variants generally present with a milder phenotype or are asymptomatic, and therefore the mode of inheritance should be kept as biallelic until the association with disease is more clear.
Cystic kidney disease v8.2 CYP24A1 Eleanor Williams reviewed gene: CYP24A1: Rating: ; Mode of pathogenicity: None; Publications: 21675912, 22337913, 24235083, 26214117, 2712945, 34307984, 38504242, 33249478; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v8.2 Achchuthan Shanmugasundram Panel types changed to Rare Disease 100K; Component Of Super Panel; GMS signed-off
Cystic kidney disease v8.1 Sarah Leigh Panel version 8.0 has been signed off on 2025-04-30
Cystic kidney disease v8.0 Sarah Leigh promoted panel to version 8.0
Cystic kidney disease v7.12 CYP24A1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CYP24A1.
Tag Q3_24_NHS_review was removed from gene: CYP24A1.
Cystic kidney disease v7.12 CYP24A1 Sarah Leigh edited their review of gene: CYP24A1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v7.11 CYP24A1 Sarah Leigh Source NHS GMS was added to CYP24A1.
Source Expert Review Green was added to CYP24A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Tag Q4_24_promote_green tag was added to gene: CFAP47.
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Classified gene: CFAP47 as Amber List (moderate evidence)
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional work) for the promotion of this gene to green rating in the next GMS update.
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Gene: cfap47 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v7.9 CFAP47 Achchuthan Shanmugasundram Phenotypes for gene: CFAP47 were changed from PKD to polycystic kidney disease, MONDO:0020642
Cystic kidney disease v7.8 CFAP47 Achchuthan Shanmugasundram Publications for gene: CFAP47 were set to PMID: 38633811
Cystic kidney disease v7.7 CFAP47 Achchuthan Shanmugasundram reviewed gene: CFAP47: Rating: GREEN; Mode of pathogenicity: None; Publications: 39698362; Phenotypes: polycystic kidney disease, MONDO:0020642; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cystic kidney disease v7.7 CFAP47 Dmitrijs Rots gene: CFAP47 was added
gene: CFAP47 was added to Cystic kidney disease. Sources: Literature
Mode of inheritance for gene: CFAP47 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CFAP47 were set to PMID: 38633811
Phenotypes for gene: CFAP47 were set to PKD
Penetrance for gene: CFAP47 were set to unknown
Mode of pathogenicity for gene: CFAP47 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CFAP47 was set to GREEN
Added comment: Three cases & some functional work described in PMID: 38633811 (now published).
Sources: Literature
Cystic kidney disease v7.7 CYS1 Arina Puzriakova Entity copied from Renal ciliopathies v3.15
Cystic kidney disease v7.7 CYS1 Arina Puzriakova gene: CYS1 was added
gene: CYS1 was added to Cystic kidney disease. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: CYS1.
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease, MONDO:0020642
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh changed review comment from: CYP24A1 variants have been associated with Hypercalcemia, infantile, 1 (OMIM:143880). PMIDs: 34307984; 22337913; 27105398; 28324001 report numerous biallelic CYP24A1 variants in cases of OMIM:143880, with the occurrence of kidney cysts. PMID: 34307984 also reports a family, where three of the members are monoallelic for CYP24A1 variants, but present with OMIM:143880 and 2/3 of these cases also have kidney cysts.; to: CYP24A1 variants have been associated with Hypercalcemia, infantile, 1 (OMIM:143880). PMIDs: 34307984; 22337913; 27105398; 28324001 report numerous biallelic CYP24A1 variants in cases of OMIM:143880, with the occurrence of kidney cysts. PMID: 34307984 also reports a family, where three of the members are monoallelic for CYP24A1 variants, but present with OMIM:143880 and 2/3 of these cases also have kidney cysts. However, as this is the only report of monoallelic variants for this gene associated with OMIM:143880, the mode of inheritance for this gene should be BIALLELIC, autosomal or pseudoautosomal.
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CYP24A1.
Tag Q3_24_NHS_review tag was added to gene: CYP24A1.
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh Phenotypes for gene: CYP24A1 were changed from cystic kidney disease; nephrocalcinosis; hypercalcaemia to Hypercalcemia, infantile, 1, OMIM:143880; hypercalcemia, infantile, 1, MONDO:0020739
Cystic kidney disease v7.5 CYP24A1 Sarah Leigh Classified gene: CYP24A1 as Amber List (moderate evidence)
Cystic kidney disease v7.5 CYP24A1 Sarah Leigh Gene: cyp24a1 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Tag watchlist tag was added to gene: COL4A3.
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Classified gene: COL4A3 as Amber List (moderate evidence)
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Added comment: Comment on list classification: There is some evidence that shows some patients with COL4A3-related Alport syndrome have multicystic kidney disease (MKD).

PMID: 38178635 - Bada-Bosch et al 2024 - at least 8 unrelated individuals with heterozygous LP/P variants in the COL4A3 and MKD.

However, a substantial proportion of AD Alport Syndrome patients maintain normal kidney function throughout life and the factors underlying the development of kidney disease remain incompletely understood.

Rating Amber given that inclusion of other Alport genes COL4A4/5 on this panel was rejected on GMS expert review but monitoring of this association should be continued (added watchlist tag).
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Gene: col4a3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v7.3 COL4A5 Arina Puzriakova Publications for gene: COL4A5 were set to 31922066
Cystic kidney disease v7.2 COL4A4 Arina Puzriakova Publications for gene: COL4A4 were set to 31922066
Cystic kidney disease v7.1 CYP24A1 John Sayer gene: CYP24A1 was added
gene: CYP24A1 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: CYP24A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYP24A1 were set to 34307984; 22337913; 27105398; 28324001
Phenotypes for gene: CYP24A1 were set to cystic kidney disease; nephrocalcinosis; hypercalcaemia
Penetrance for gene: CYP24A1 were set to Complete
Review for gene: CYP24A1 was set to GREEN
Added comment: Can give cystic kidney disease (mild, atypical) but useful to be added to R193 panel
Sources: Expert list
Cystic kidney disease v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2024-10-30
Cystic kidney disease v7.0 Arina Puzriakova promoted panel to version 7.0
Cystic kidney disease v6.3 CLCN5 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: CLCN5.
Tag Q2_24_NHS_review was removed from gene: CLCN5.
Cystic kidney disease v6.3 CLCN5 Achchuthan Shanmugasundram reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cystic kidney disease v6.2 CLCN5 Achchuthan Shanmugasundram Source NHS GMS was added to CLCN5.
Source Expert Review Green was added to CLCN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-08-07
Cystic kidney disease v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Cystic kidney disease v5.8 COL4A3 John Sayer changed review comment from: evidence pointing for CDOL4A3/4/5 causing mild cystic phenotypes
Sources: Research; to: evidence pointing for COL4A3/4/5 causing mild cystic phenotypes
Sources: Research
Cystic kidney disease v5.8 COL4A3 John Sayer gene: COL4A3 was added
gene: COL4A3 was added to Cystic kidney disease. Sources: Research
Mode of inheritance for gene: COL4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3 were set to 38178635; 35602506
Phenotypes for gene: COL4A3 were set to cystic kidney disease; proteinuria; haematuria
Penetrance for gene: COL4A3 were set to Incomplete
Review for gene: COL4A3 was set to RED
Added comment: evidence pointing for CDOL4A3/4/5 causing mild cystic phenotypes
Sources: Research
Cystic kidney disease v5.8 COL4A4 John Sayer changed review comment from: may phenocopy PKD1
Sources: Other; to: may phenocopy PKD1
Sources: Other


additional new publication
PMID: 38178635
Cystic kidney disease v5.8 COL4A5 John Sayer commented on gene: COL4A5: Additional publication supporting this gene with cystic kidney phenotypes
PMID: 38680391
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram edited their review of gene: OFD1: Changed rating: AMBER; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although renal cysts are present in around half of the cases reported in PMID:11179005 (and associated with Orofaciodigital syndrome I, MIM #311200), they are syndromic cases./

As reviewed by Nour Elkhateeb, female patient reported in PMID:10910455 had renal cysts are the only apparent manifestation.

Hence, this gene can be promoted from red to amber with the current evidence.; to: Comment on list classification: Although renal cysts are present in around half of the cases reported in PMID:11179005 (and associated with Orofaciodigital syndrome I, MIM #311200), they are syndromic.

As reviewed by Nour Elkhateeb, female patient reported in PMID:10910455 had renal cysts are the only apparent manifestation.

Hence, this gene can be promoted from red to amber with the current evidence.
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram Classified gene: OFD1 as Amber List (moderate evidence)
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although renal cysts are present in around half of the cases reported in PMID:11179005 (and associated with Orofaciodigital syndrome I, MIM #311200), they are syndromic cases./

As reviewed by Nour Elkhateeb, female patient reported in PMID:10910455 had renal cysts are the only apparent manifestation.

Hence, this gene can be promoted from red to amber with the current evidence.
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v5.7 OFD1 Achchuthan Shanmugasundram Publications for gene: OFD1 were set to
Cystic kidney disease v5.6 CLCN5 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: CLCN5.
Tag Q2_24_NHS_review tag was added to gene: CLCN5.
Cystic kidney disease v5.6 CLCN5 Sarah Leigh Publications for gene: CLCN5 were set to 7922301; 37641036
Cystic kidney disease v5.5 CLCN5 Sarah Leigh reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: None; Publications: 8559248, 9259268, 9187673, 9602200, 14569459, 16041495, 16247550, 19673950; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v5.5 CLCN5 Sarah Leigh Phenotypes for gene: CLCN5 were changed from cystic kdiney disease; cortical cysts; medullary cysts; nephrocalcinosis; low molecular weight proteinuria; hypercalciuria to Dent disease 1, OMIM:300009; Hypophosphatemic rickets, OMIM:300554; Nephrolithiasis, type I, OMIM:310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, OMIM:308990
Cystic kidney disease v5.4 CLCN5 Sarah Leigh Classified gene: CLCN5 as Amber List (moderate evidence)
Cystic kidney disease v5.4 CLCN5 Sarah Leigh Gene: clcn5 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v5.3 NEK8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NEK8.
Cystic kidney disease v5.3 SEC63 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SEC63.
Tag Q3_23_NHS_review was removed from gene: SEC63.
Cystic kidney disease v5.3 PRKCSH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PRKCSH.
Tag Q3_23_NHS_review was removed from gene: PRKCSH.
Cystic kidney disease v5.3 SEC63 Arina Puzriakova reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.3 PRKCSH Arina Puzriakova reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.3 NEK8 Arina Puzriakova reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.2 SEC63 Achchuthan Shanmugasundram Source Expert Review Green was added to SEC63.
Source NHS GMS was added to SEC63.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.2 PRKCSH Achchuthan Shanmugasundram Source Expert Review Green was added to PRKCSH.
Source NHS GMS was added to PRKCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.2 NEK8 Achchuthan Shanmugasundram Source Expert Review Green was added to NEK8.
Source NHS GMS was added to NEK8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Cystic kidney disease v5.0 Eleanor Williams promoted panel to version 5.0
Cystic kidney disease v4.24 CLCN5 John Sayer gene: CLCN5 was added
gene: CLCN5 was added to Cystic kidney disease. Sources: Literature
Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CLCN5 were set to 7922301; 37641036
Phenotypes for gene: CLCN5 were set to cystic kdiney disease; cortical cysts; medullary cysts; nephrocalcinosis; low molecular weight proteinuria; hypercalciuria
Penetrance for gene: CLCN5 were set to Complete
Review for gene: CLCN5 was set to GREEN
Added comment: Oliver Wrong noted kidney cysts in 33% of his cohort and I think Dent disease is such a difficult diagnosis to make, adding it to the cystic panel will identify new cases presenting with mild cystic kidney disease
Sources: Literature
Cystic kidney disease v4.24 OFD1 Nour Elkhateeb changed review comment from: OFD1 appears to be highly penetrant, although highly variable in expression. In some reports, renal cysts are the only apparent manifestation in affected females. PMID: 10910455.; to: OFD1 appears to be highly penetrant, although highly variable in expression. In some reports, renal cysts are the only apparent manifestation in affected females. PMID: 10910455.
Cystic kidney disease v4.24 OFD1 Nour Elkhateeb reviewed gene: OFD1: Rating: ; Mode of pathogenicity: None; Publications: PMID: 10910455; Phenotypes: renal cysts; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: NEK8.
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Classified gene: NEK8 as Amber List (moderate evidence)
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available in support of the association of monoallelic NEK8 variants with polycystic kidney disease. Hence, this gene can be promoted to green rating in the next GMS review.
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Gene: nek8 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.23 NEK8 Achchuthan Shanmugasundram Mode of inheritance for gene: NEK8 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.22 NEK8 Achchuthan Shanmugasundram edited their review of gene: NEK8: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cystic kidney disease v4.22 NEK8 Achchuthan Shanmugasundram changed review comment from: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8.

PMID:18199800 reported one patient with biallelic NEK8 variant (p.His425Tyr) and with nephronophthisis. Nephronophthisis is an autosomal recessive kidney disease that leads to kidney cyst formation and progressive renal failure.

Although nephronophthisis 9 (MIM #613824) caused by biallelic variants is reported in both OMIM and Gene2Phenotype, cystic kidney disease caused by monoallelic variants are not yet reported in these resources.; to: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8. Carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF and these variants are suspected of dominant negative effect.

PMID:18199800 reported one patient with biallelic NEK8 variant (p.His425Tyr) and with nephronophthisis. Nephronophthisis is an autosomal recessive kidney disease that leads to kidney cyst formation and progressive renal failure.

Although nephronophthisis 9 (MIM #613824) caused by biallelic variants is reported in both OMIM and Gene2Phenotype, cystic kidney disease caused by monoallelic variants are not yet reported in these resources.
Cystic kidney disease v4.22 NEK8 Achchuthan Shanmugasundram Mode of pathogenicity for gene: NEK8 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cystic kidney disease v4.21 NEK8 Achchuthan Shanmugasundram Publications for gene: NEK8 were set to
Cystic kidney disease v4.20 NEK8 Achchuthan Shanmugasundram Phenotypes for gene: NEK8 were changed from Ciliopathy genes associated with cystic kidney disease to polycystic kidney disease, MONDO:0020642; ?Nephronophthisis 9, OMIM:613824
Cystic kidney disease v4.19 NEK8 Achchuthan Shanmugasundram changed review comment from: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8.; to: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8.

PMID:18199800 reported one patient with biallelic NEK8 variant (p.His425Tyr) and with nephronophthisis. Nephronophthisis is an autosomal recessive kidney disease that leads to kidney cyst formation and progressive renal failure.

Although nephronophthisis 9 (MIM #613824) caused by biallelic variants is reported in both OMIM and Gene2Phenotype, cystic kidney disease caused by monoallelic variants are not yet reported in these resources.
Cystic kidney disease v4.19 NEK8 Achchuthan Shanmugasundram edited their review of gene: NEK8: Changed publications to: 18199800, 37598857; Changed phenotypes to: polycystic kidney disease, MONDO:0020642, ?Nephronophthisis 9, OMIM:613824
Cystic kidney disease v4.19 NEK8 Achchuthan Shanmugasundram reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37598857; Phenotypes: polycystic kidney disease, MONDO:0020642; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.17 NEK8 Dmitrijs Rots reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 37598857; Phenotypes: polycystic kidney disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.17 TULP3 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: TULP3.
Tag Q2_23_NHS_review was removed from gene: TULP3.
Cystic kidney disease v4.17 ALG5 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: ALG5.
Tag Q1_23_NHS_review was removed from gene: ALG5.
Cystic kidney disease v4.17 TULP3 Achchuthan Shanmugasundram commented on gene: TULP3: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Cystic kidney disease v4.17 ALG5 Achchuthan Shanmugasundram reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v4.16 TULP3 Achchuthan Shanmugasundram Source Expert Review Green was added to TULP3.
Source NHS GMS was added to TULP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v4.16 ALG5 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG5.
Source NHS GMS was added to ALG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v4.15 SEC63 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SEC63.
Tag Q3_23_NHS_review tag was added to gene: SEC63.
Cystic kidney disease v4.15 SEC63 Achchuthan Shanmugasundram Classified gene: SEC63 as Amber List (moderate evidence)
Cystic kidney disease v4.15 SEC63 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ian Berry, this gene should be considered for green rating in this panel in the next GMS review as there are sufficient cases of polycystic liver disease 2 with both renal and hepatic cysts.
Cystic kidney disease v4.15 SEC63 Achchuthan Shanmugasundram Gene: sec63 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.14 SEC63 Achchuthan Shanmugasundram Publications for gene: SEC63 were set to 15133510,
Cystic kidney disease v4.13 SEC63 Achchuthan Shanmugasundram Publications for gene: SEC63 were set to
Cystic kidney disease v4.12 SEC63 Achchuthan Shanmugasundram Phenotypes for gene: SEC63 were changed from to Polycystic liver disease 2 with or without kidney cysts, OMIM:617004
Cystic kidney disease v4.11 SEC63 Achchuthan Shanmugasundram Mode of inheritance for gene: SEC63 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.10 SEC63 Achchuthan Shanmugasundram reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: None; Publications: 24886261; Phenotypes: Polycystic liver disease 2 with or without kidney cysts, OMIM:617004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.10 PRKCSH Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Ian Berry, this gene should be considered for green rating in this panel in the next GMS review as there are sufficient cases of polycystic liver disease 1 with renal cysts.; to: Comment on list classification: As reviewed by Ian Berry, this gene should be considered for green rating in this panel in the next GMS review as there are sufficient cases of polycystic liver disease 1 with both renal and hepatic cysts.
Cystic kidney disease v4.10 PRKCSH Achchuthan Shanmugasundram Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1 with or without kidney cysts, OMIM:174050
Cystic kidney disease v4.9 PRKCSH Achchuthan Shanmugasundram Publications for gene: PRKCSH were set to 12529853; 12577059; 24886261
Cystic kidney disease v4.9 PRKCSH Achchuthan Shanmugasundram Publications for gene: PRKCSH were set to
Cystic kidney disease v4.8 PRKCSH Achchuthan Shanmugasundram Mode of inheritance for gene: PRKCSH was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.7 PRKCSH Achchuthan Shanmugasundram Classified gene: PRKCSH as Amber List (moderate evidence)
Cystic kidney disease v4.7 PRKCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ian Berry, this gene should be considered for green rating in this panel in the next GMS review as there are sufficient cases of polycystic liver disease 1 with renal cysts.
Cystic kidney disease v4.7 PRKCSH Achchuthan Shanmugasundram Gene: prkcsh has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.6 PRKCSH Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PRKCSH.
Tag Q3_23_NHS_review tag was added to gene: PRKCSH.
Cystic kidney disease v4.6 PRKCSH Achchuthan Shanmugasundram reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24886261; Phenotypes: Polycystic liver disease 1 with or without kidney cysts, OMIM:174050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.6 PRKCSH Ian Berry changed review comment from: Phenotype is predominantly hepatic but can involve renal cysts.

We have seen 2x patients with pathogenic findings in this gene through R193 referrals therefore it makes sense to be on this panel. R193 referrals frequently have both renal & hepatic cysts.; to: Phenotype is predominantly hepatic but can involve renal cysts.

We have seen 2x patients with pathogenic findings in this gene through R193 referrals therefore it makes sense to be on this panel. R193 referrals frequently have both renal & hepatic cysts.

OMIM disorder name is polycystic liver disease-1 with or without kidney cysts (PCLD1)
Cystic kidney disease v4.6 SEC63 Ian Berry changed review comment from: Phenotype is predominantly hepatic but can involve renal cysts.

We have seen 2x patients with pathogenic findings in this gene through R193 referrals therefore it makes sense to be on this panel. R193 referrals frequently have both renal & hepatic cysts.; to: Phenotype is predominantly hepatic but can involve renal cysts.

We have seen 2x patients with pathogenic findings in this gene through R193 referrals therefore it makes sense to be on this panel. R193 referrals frequently have both renal & hepatic cysts.

OMIM disorder name is polycystic liver disease-2 with or without kidney cysts (PCLD2)
Cystic kidney disease v4.6 SEC63 Ian Berry reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.6 PRKCSH Ian Berry reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.6 DZIP1L Eleanor Williams commented on gene: DZIP1L
Cystic kidney disease v4.6 DZIP1L Eleanor Williams Phenotypes for gene: DZIP1L were changed from ARPKD; Polycystic kidney disease 5 617610 to Polycystic kidney disease 5, OMIM:617610; polycystic kidney disease 5, MONDO_0033281
Cystic kidney disease v4.5 DZIP1L Eleanor Williams Publications for gene: DZIP1L were set to 28530676
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.; to: Comment on list classification: As reviewed by John Sayer, there is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram changed review comment from: PMID:35397207 reported individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which individuals from six families had kidney abnormalities including presentation of kidney cysts in at least an individual from five families. In addition, experiments in TULP3 knockout zebrafish models recapitulated the phenotypes observed in patients including the kidney cysts.

PMID:36276950 reported two sisters with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (p.Arg382Trp). In addition, experiments with inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant showed that this variant had a severely reduced ability to localise membrane-associated proteins to the cilium, consistent with a loss of TULP3 function.

PMID:36460032 reported two cases with biallelic variants in TULP3 (patient A: homozygous; patient B: compound heterozygous) and both had cystic kidney disease.

Functional studies from mouse models also showed that knockout mice developed cystic kidney disease (PMIDs: 30799239 & 30799240).; to: PMID:35397207 reported individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which individuals from six families had kidney abnormalities including presentation of kidney cysts in at least an individual from five families. In addition, experiments in TULP3 knockout zebrafish models recapitulated the phenotypes observed in patients including the kidney cysts.

PMID:36276950 reported two sisters with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (p.Arg382Trp). In addition, experiments with inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant showed that this variant had a severely reduced ability to localise membrane-associated proteins to the cilium, consistent with a loss of TULP3 function.

PMID:36460032 reported two cases with biallelic variants in TULP3 (patient A: homozygous; patient B: compound heterozygous) and both had cystic kidney disease.

Functional studies from mouse models also showed that knockout mice developed cystic kidney disease (PMIDs: 30799239 & 30799240).

This gene has been associated with relevant phenotypes in OMIM (MIM #619902), but not in Gene2Phenotype.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TULP3.
Tag Q2_23_NHS_review tag was added to gene: TULP3.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Deleted their comment
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Deleted their comment
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.3 TULP3 Achchuthan Shanmugasundram Phenotypes for gene: TULP3 were changed from cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy to Hepatorenocardiac degenerative fibrosis, OMIM:619902
Cystic kidney disease v4.2 TULP3 Achchuthan Shanmugasundram Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Cystic kidney disease v4.1 TULP3 Achchuthan Shanmugasundram reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30799239, 30799240, 35397207, 36276950, 36460032; Phenotypes: Hepatorenocardiac degenerative fibrosis, OMIM:619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v4.1 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Phenotypes for gene: TULP3 were set to cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to GREEN
Added comment: TULP3 is a novel human cilipathy gene (OMIM 604730)
Hepatorenocardiac degenerative fibrosis is OMIM pehnotype
Cystic kidney disease is a typical feature
Sources: Expert list
Cystic kidney disease v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Cystic kidney disease v4.0 Eleanor Williams promoted panel to version 4.0
Cystic kidney disease v3.9 ALG5 Arina Puzriakova Classified gene: ALG5 as Amber List (moderate evidence)
Cystic kidney disease v3.9 ALG5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Cystic kidney disease v3.9 ALG5 Arina Puzriakova Gene: alg5 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v3.8 ALG5 Arina Puzriakova gene: ALG5 was added
gene: ALG5 was added to Cystic kidney disease. Sources: Literature
Q1_23_promote_green, Q1_23_NHS_review tags were added to gene: ALG5.
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Polycystic kidney disease 7, OMIM:620056
Review for gene: ALG5 was set to GREEN
Added comment: New gene suggested for this panel by Prof John Sayer (Newcastle Hospitals NHS Foundation Trust). Associated with a relevant phenotype in OMIM (MIM# 620056) but is not yet listed in G2P.

Lemoine et al., 2022 (PMID: 35896117) reported 19 patients from 5 unrelated families with adult-onset polycystic kidney disease and monoallelic variants in this gene. Affected individuals had non-enlarged cystic kidneys and few or no liver cysts, and some patients reached end-stage kidney disease from 62 to 91 years of age.
Sources: Literature
Cystic kidney disease v3.7 ANKS6 Achchuthan Shanmugasundram Added comment: Comment on publications: Additional cases (two affected siblings identified with biallelic ANKS6 variants and reported with late-onset chronic kidney disease) and functional studies in PMID:34740236.
Cystic kidney disease v3.7 ANKS6 Achchuthan Shanmugasundram Publications for gene: ANKS6 were set to
Cystic kidney disease v3.6 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 16, OMIM:615382 to Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 16, OMIM:615382
Cystic kidney disease v3.5 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 16, OMIM:615382
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ZNF423.
Tag Q3_22_expert_review was removed from gene: ZNF423.
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram edited their review of gene: ZNF423: Changed rating: AMBER
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.
Cystic kidney disease v3.4 IFT140 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: IFT140.
Tag Q2_22_NHS_review was removed from gene: IFT140.
Cystic kidney disease v3.4 XPNPEP3 Achchuthan Shanmugasundram Tag Q2_21_expert_review was removed from gene: XPNPEP3.
Tag Q1_22_rating was removed from gene: XPNPEP3.
Tag Q1_22_phenotype was removed from gene: XPNPEP3.
Cystic kidney disease v3.4 PAX2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: PAX2.
Tag Q3_22_NHS_review was removed from gene: PAX2.
Cystic kidney disease v3.4 GLA Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: GLA.
Tag Q3_22_NHS_review was removed from gene: GLA.
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram reviewed gene: ZNF423: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 IFT140 Achchuthan Shanmugasundram reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 XPNPEP3 Achchuthan Shanmugasundram reviewed gene: XPNPEP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 PAX2 Achchuthan Shanmugasundram reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 GLA Achchuthan Shanmugasundram reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.3 XPNPEP3 Achchuthan Shanmugasundram Source Expert Review Green was added to XPNPEP3.
Source NHS GMS was added to XPNPEP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.3 PAX2 Achchuthan Shanmugasundram Source Expert Review Green was added to PAX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.3 IFT140 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT140.
Source NHS GMS was added to IFT140.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.3 GLA Achchuthan Shanmugasundram Source Expert Review Green was added to GLA.
Source NHS GMS was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.2 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to
Cystic kidney disease v3.1 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Cystic kidney disease v3.0 Catherine Snow promoted panel to version 3.0
Cystic kidney disease v2.53 ZNF423 Eleanor Williams commented on gene: ZNF423
Cystic kidney disease v2.53 ZNF423 Eleanor Williams Tag Q1_22_expert_review was removed from gene: ZNF423.
Tag Q3_22_rating tag was added to gene: ZNF423.
Tag Q3_22_expert_review tag was added to gene: ZNF423.
Cystic kidney disease v2.53 TTC21B Eleanor Williams commented on gene: TTC21B
Cystic kidney disease v2.53 TTC21B Eleanor Williams Tag watchlist_moi tag was added to gene: TTC21B.
Cystic kidney disease v2.53 GLA Eleanor Williams Added comment: Comment on mode of inheritance: There is evidence that heterozyous females are not always asymptomatic carriers, with renal disease being reported as part of the phenotype in several cases (PMID: 17224688 Wang et al 2007, PMID: 29770213 McCloskey et al 2018).
Cystic kidney disease v2.53 GLA Eleanor Williams Mode of inheritance for gene: GLA was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cystic kidney disease v2.52 GLA Eleanor Williams Phenotypes for gene: GLA were changed from to Fabry disease, OMIM:301500; Fabry disease, MONDO:0010526; Renal cyst, HP:0000107; renal parapelvic cysts
Cystic kidney disease v2.51 GLA Eleanor Williams Publications for gene: GLA were set to
Cystic kidney disease v2.50 GLA Eleanor Williams Classified gene: GLA as Amber List (moderate evidence)
Cystic kidney disease v2.50 GLA Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber but with a recommendation for a green rating following GMS review. More than 3 cases reported with renal parapelvic cysts.
Cystic kidney disease v2.50 GLA Eleanor Williams Gene: gla has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.49 GLA Eleanor Williams Tag Q3_22_rating tag was added to gene: GLA.
Tag Q3_22_NHS_review tag was added to gene: GLA.
Cystic kidney disease v2.49 GLA Eleanor Williams commented on gene: GLA
Cystic kidney disease v2.49 PAX2 Eleanor Williams changed review comment from: As reviewer notes PAX2 is associated with Papillorenal syndrome #120330 (AD) in OMIM and Renal cysts and Multicystic dysplastic kidneys are listed as clinical features.

In PMID: 22213154 Bowers et al 2012 review of PAX2 variants found in patients with renal coloboma syndrome they note that renal cysts were found in 8% of patients (n = 13), and multicystic dysplastic kidneys in 6% (n = 7) from more than three unrelated families.

Deng et al 2019 - PMID: 31060108 examined the phenotypes of 10 children (one was Mongolian and the rest were of Han Chinese ethnicity) with PAX2 variants. Renal cysts were detected in five patients.; to: As reviewer notes PAX2 is associated with Papillorenal syndrome #120330 (AD) in OMIM and Renal cysts and Multicystic dysplastic kidneys are listed as clinical features.

In PMID: 22213154 Bowers et al 2012 review of PAX2 variants found in patients with renal coloboma syndrome they note that renal cysts were found in 8% of patients (n = 13), and multicystic dysplastic kidneys in 6% (n = 7) from more than three unrelated families.

Deng et al 2019 - PMID: 31060108 examined the phenotypes of 10 children (one was Mongolian and the rest were of Han Chinese ethnicity) with PAX2 variants. Renal cysts were detected in five patients.

A further case of cystic renal disease in a patient with PAX2 variants are reported in PMID: 22213154
Cystic kidney disease v2.49 PAX2 Eleanor Williams Publications for gene: PAX2 were set to PMID: 33746522; 16049068; 22213154
Cystic kidney disease v2.48 PAX2 Eleanor Williams Phenotypes for gene: PAX2 were changed from cystic renal disease to Papillorenal syndrome, OMIM:120330; renal coloboma syndrome, MONDO:0007352
Cystic kidney disease v2.47 PAX2 Eleanor Williams Mode of inheritance for gene: PAX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.46 PAX2 Eleanor Williams Classified gene: PAX2 as Amber List (moderate evidence)
Cystic kidney disease v2.46 PAX2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber with a recommendation for green rating following GMS review. There are more than 3 cases reported where renal cysts are part of the phenotype.
Cystic kidney disease v2.46 PAX2 Eleanor Williams Gene: pax2 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.45 PAX2 Eleanor Williams Tag Q3_22_rating tag was added to gene: PAX2.
Tag Q3_22_NHS_review tag was added to gene: PAX2.
Cystic kidney disease v2.45 PAX2 Eleanor Williams reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22213154, 31060108; Phenotypes: Papillorenal syndrome, OMIM:120330, renal coloboma syndrome, MONDO:0007352; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.45 PAX2 Natalie Forrester gene: PAX2 was added
gene: PAX2 was added to Cystic kidney disease. Sources: NHS GMS
Mode of inheritance for gene: PAX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX2 were set to PMID: 33746522; 16049068; 22213154
Phenotypes for gene: PAX2 were set to cystic renal disease
Penetrance for gene: PAX2 were set to unknown
Review for gene: PAX2 was set to GREEN
gene: PAX2 was marked as current diagnostic
Added comment: PAX2 (OMIM 167409) is associated with Papillorenal syndrome, one feature of which can be renal cysts. Ocular involvement is common, but it is also noted that it can be mild/undetectable. In our NHSE lab we have identified a novel missense variant in a patient with cystic dysplastic kidneys. This was detected by Exomiser tiering by WGS and was reported as likely pathogenic. There are many reports in the literature of its association with renal disease, including cysts, and I expect that is the reason it is included on the R195 and R257 panels, but it also seems appropriate to be included on R193 where currently it is not even amber or red.
Sources: NHS GMS
Cystic kidney disease v2.45 IFT140 John Sayer reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890546; Phenotypes: cystic kidney disease, cystic liver disease; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cystic kidney disease v2.45 GLA John Sayer reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29770213, 28371803, 27061865, 21290670, 15327390, 15091117; Phenotypes: renal parapelvic cysts, renal cortical cysts; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cystic kidney disease v2.45 XPNPEP3 Eleanor Williams Tag Q2_21_expert_review tag was added to gene: XPNPEP3.
Cystic kidney disease v2.45 IFT140 Eleanor Williams Tag Q2_22_NHS_review tag was added to gene: IFT140.
Cystic kidney disease v2.45 IFT140 Eleanor Williams Tag Q2_22_rating tag was added to gene: IFT140.
Cystic kidney disease v2.45 IFT140 Eleanor Williams Classified gene: IFT140 as Amber List (moderate evidence)
Cystic kidney disease v2.45 IFT140 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber with a recommendation for GREEN rating following GMS review.
Cystic kidney disease v2.45 IFT140 Eleanor Williams Gene: ift140 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.44 IFT140 Eleanor Williams Phenotypes for gene: IFT140 were changed from Cystic kidney disease; chronic kidney disease to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920; short-rib thoracic dysplasia 9 with or without polydactyly, MONDO:0009964; cystic kidney disease, MONDO:0002473
Cystic kidney disease v2.43 IFT140 Eleanor Williams Publications for gene: IFT140 were set to 34890546
Cystic kidney disease v2.42 IFT140 Eleanor Williams Added comment: Comment on mode of inheritance: As reviewer notes there are several biallelic cases reported with a renal phenotype (e.g. PMID: 23418020 - 3 patients with renal cysts and biallelic IFT140 variants, PMID: 27874174 - 1 patient with renal cysts and biallelic IFT140 variants) aswell as the monallelic variants reported in PMID:34890546
Cystic kidney disease v2.42 IFT140 Eleanor Williams Mode of inheritance for gene: IFT140 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cystic kidney disease v2.41 ZNF423 Arina Puzriakova commented on gene: ZNF423: There are now two unrelated families with homozygous variants and two cases with heterozygous variants in this gene associated with nephronophthisis or Joubert syndrome. Zfp423-mutant mice harbouring some variants (but not all - including one patient variant) displayed neuroanatomical abnormalities that were consistent with the human phenotype. Overall the evidence is borderline and therefore this gene will be flagged for GMS expert review to determine whether it should be upgraded to green at this stage.
Cystic kidney disease v2.41 ZNF423 Arina Puzriakova reviewed gene: ZNF423: Rating: ; Mode of pathogenicity: None; Publications: 22863007, 32925911, 33323469; Phenotypes: Joubert syndrome 19, OMIM:614844, Nephronophthisis 14, OMIM:614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cystic kidney disease v2.41 ZNF423 Arina Puzriakova Tag Q1_22_expert_review tag was added to gene: ZNF423.
Cystic kidney disease v2.41 ZNF423 Arina Puzriakova Classified gene: ZNF423 as Amber List (moderate evidence)
Cystic kidney disease v2.41 ZNF423 Arina Puzriakova Gene: znf423 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.40 ZNF423 Arina Puzriakova Publications for gene: ZNF423 were set to
Cystic kidney disease v2.39 ZNF423 Arina Puzriakova Mode of inheritance for gene: ZNF423 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cystic kidney disease v2.38 ZNF423 Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Ciliopathy genes associated with cystic kidney disease to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
Cystic kidney disease v2.37 ALG8 Sarah Leigh Publications for gene: ALG8 were set to 30135240; 28375157
Cystic kidney disease v2.36 ALG8 Sarah Leigh reviewed gene: ALG8: Rating: ; Mode of pathogenicity: None; Publications: 15235028; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v2.36 ISCA-37432-Loss Arina Puzriakova commented on Region: ISCA-37432-Loss
Cystic kidney disease v2.36 ISCA-37405-Loss Arina Puzriakova commented on Region: ISCA-37405-Loss
Cystic kidney disease v2.36 ISCA-37405-Loss Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181.
Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30.
Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
Cystic kidney disease v2.36 ISCA-37432-Loss Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616.
Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
Cystic kidney disease v2.35 DZIP1L Yu Leng Phua Deleted their comment
Cystic kidney disease v2.35 DZIP1L Yu Leng Phua edited their review of gene: DZIP1L: Added comment: Four children from three consanguineous families presenting with polycystic kidney disease;
Variants: c.193 T > C; p.(Cys65Arg), and c.216C > G; p.(Cys72Trp);
Functional analyses of the c.216C > G; p.(Cys72Trp) variant indicated mislocalization of mutant DZIP1L;
NOTE: Lack of liver phenotype in these patients; Changed phenotypes to: # 617610 POLYCYSTIC KIDNEY DISEASE 5, PKD5
Cystic kidney disease v2.35 DZIP1L Yu Leng Phua reviewed gene: DZIP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 35211789; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v2.35 FLCN Eleanor Williams Tag Q2_21_rating was removed from gene: FLCN.
Tag Q2_21_NHS_review was removed from gene: FLCN.
Cystic kidney disease v2.35 FLCN Eleanor Williams commented on gene: FLCN: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Cystic kidney disease v2.34 FLCN Eleanor Williams Source Expert Review Green was added to FLCN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v2.33 COL4A4 Eleanor Williams Tag for-review was removed from gene: COL4A4.
Cystic kidney disease v2.33 ALG9 Eleanor Williams Tag for-review was removed from gene: ALG9.
Cystic kidney disease v2.33 ALG8 Eleanor Williams Tag for-review was removed from gene: ALG8.
Cystic kidney disease v2.33 SEC61A1 Eleanor Williams commented on gene: SEC61A1: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Cystic kidney disease v2.33 COL4A4 Eleanor Williams commented on gene: COL4A4: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. The reviewers note that only 1 patient reported where they would be classed as AD-PKD. The other 3 are primarily TBMN patients who also have renal cysts.
Cystic kidney disease v2.33 ALG9 Eleanor Williams commented on gene: ALG9: The rating and mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Cystic kidney disease v2.33 ALG8 Eleanor Williams commented on gene: ALG8: The rating and mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Cystic kidney disease v2.32 SEC61A1 Eleanor Williams Source Expert list was added to SEC61A1.
Cystic kidney disease v2.32 ALG9 Eleanor Williams Source Expert Review Green was added to ALG9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v2.32 ALG8 Eleanor Williams Source Expert Review Green was added to ALG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v2.31 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 34890546; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, MONDO:0009964, Cystic Kidney Disease, MONDO# 0002473, IFT140-related, dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cystic kidney disease v2.31 IFT140 Anna de Burca reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890546; Phenotypes: Autosomal dominant polycystic kidney disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
Tag Q1_22_phenotype tag was added to gene: XPNPEP3.
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, depending on review of the phenotype.
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.30 XPNPEP3 Sarah Leigh Mode of inheritance for gene: XPNPEP3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v2.29 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to
Cystic kidney disease v2.28 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Ciliopathy genes associated with cystic kidney disease to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Cystic kidney disease v2.27 IFT140 Daniel Gale gene: IFT140 was added
gene: IFT140 was added to Cystic kidney disease. Sources: Literature,Research
Mode of inheritance for gene: IFT140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFT140 were set to 34890546
Phenotypes for gene: IFT140 were set to Cystic kidney disease; chronic kidney disease
Penetrance for gene: IFT140 were set to unknown
Review for gene: IFT140 was set to GREEN
Added comment: Very strong evidence of association of truncating IFT140 mutations and cystic kidney disease in cited paper, which includes 12 multiplex families and 26 singletons. In addition, hypothesis-free region-based variance testing (SKAT-O) independently identifying truncating variants in this gene in 100,000 Genomes Project (p=3.5e-17) and UK BioBank (p=4.5e-15) participants with cystic kidney disease (see https://genebass.org/gene/undefined/phenotype/icd_first_occurrence-132532-both_sexes--?resultIndex=gene-manhattan&resultLayout=full for UKBB analysis).
Sources: Literature, Research
Cystic kidney disease v2.27 FLCN Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: FLCN.
Cystic kidney disease v2.27 COL4A4 Arina Puzriakova Phenotypes for gene: COL4A4 were changed from Cystic kidney disease, MONDO:0002473 to Cystic kidney disease, MONDO:0002473
Cystic kidney disease v2.27 COL4A4 Arina Puzriakova Phenotypes for gene: COL4A4 were changed from cystic kidney disease MONDO:0002473 to Cystic kidney disease, MONDO:0002473
Cystic kidney disease v2.26 FLCN Eleanor Williams Classified gene: FLCN as Amber List (moderate evidence)
Cystic kidney disease v2.26 FLCN Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, with a recommendation for green rating at the next GMS review.
Cystic kidney disease v2.26 FLCN Eleanor Williams Gene: flcn has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.25 FLCN Eleanor Williams Tag Q2_21_rating tag was added to gene: FLCN.
Cystic kidney disease v2.25 FLCN Eleanor Williams commented on gene: FLCN
Cystic kidney disease v2.25 FLCN Eleanor Williams Publications for gene: FLCN were set to PMID: 19785621; 31266032
Cystic kidney disease v2.24 FLCN Eleanor Williams Phenotypes for gene: FLCN were changed from renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma to Birt-Hogg-Dube syndrome, OMIM:135150; renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma
Cystic kidney disease v2.23 FLCN Daniel Gale gene: FLCN was added
gene: FLCN was added to Cystic kidney disease. Sources: Literature,Expert Review
Mode of inheritance for gene: FLCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FLCN were set to PMID: 19785621; 31266032
Phenotypes for gene: FLCN were set to renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma
Penetrance for gene: FLCN were set to Incomplete
Review for gene: FLCN was set to GREEN
Added comment: Birt Hogg Dube syndrome (caused by variants in FLCN) is frequently associated with multiple renal cysts, without renal enlargement or progressive CKD. Previous published data indicate simple renal cysts present in 31-45% (PMID: 31266032;19785621) of patients with BHD and audit of 20 patients I follow up revealed simple renal cysts in 11 (multiple in 9 of these individuals) i.e. similar to the literature. Therefore BHD should be considered in the differential diagnosis of multiple renal cysts (without renal enlargement).
Sources: Literature, Expert Review
Cystic kidney disease v2.23 COL4A5 Eleanor Williams commented on gene: COL4A5: Removed 'for-review' tag as only 1 case, so red rating.
Cystic kidney disease v2.23 COL4A5 Eleanor Williams Tag for-review was removed from gene: COL4A5.
Cystic kidney disease v2.23 COL4A4 Eleanor Williams edited their review of gene: COL4A4: Changed rating: GREEN
Cystic kidney disease v2.23 COL4A4 Ivone Leong Tag for-review tag was added to gene: COL4A4.
Cystic kidney disease v2.23 COL4A5 Eleanor Williams Tag for-review tag was added to gene: COL4A5.
Cystic kidney disease v2.23 COL4A5 Eleanor Williams Phenotypes for gene: COL4A5 were changed from cystic kidney disease to cystic kidney disease MONDO:0002473
Cystic kidney disease v2.22 COL4A5 Eleanor Williams Classified gene: COL4A5 as Red List (low evidence)
Cystic kidney disease v2.22 COL4A5 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to red, as there is one reported case. But noting the green review from expert reviewer John Sayer, marking this gene as 'for-review' by the GMS.
Cystic kidney disease v2.22 COL4A5 Eleanor Williams Gene: col4a5 has been classified as Red List (Low Evidence).
Cystic kidney disease v2.21 COL4A5 Eleanor Williams changed review comment from: PMID: 31922066 - Gulati et al 2019 - through WES they identified 1 female patient with Thin glomerular basement membrane (TBM) disease and bilateral kidney cysts was heterozygous for a COL4A5 likely pathogenic missense variant (c.C899T: p. P300L); to: PMID: 31922066 - Gulati et al 2019 - through WES they identified 1 female patient with Thin glomerular basement membrane (TBM) disease and bilateral kidney cysts that was heterozygous for a COL4A5 likely pathogenic missense variant (c.C899T: p. P300L)
Cystic kidney disease v2.21 COL4A5 Eleanor Williams reviewed gene: COL4A5: Rating: ; Mode of pathogenicity: None; Publications: 31922066; Phenotypes: cystic kidney disease MONDO:0002473; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cystic kidney disease v2.21 COL4A4 Eleanor Williams Classified gene: COL4A4 as Amber List (moderate evidence)
Cystic kidney disease v2.21 COL4A4 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but there are 3 cases so could be promoted to green following GMS review.
Cystic kidney disease v2.21 COL4A4 Eleanor Williams Gene: col4a4 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.20 COL4A4 Eleanor Williams Phenotypes for gene: COL4A4 were changed from cystic kidney disease to cystic kidney disease MONDO:0002473
Cystic kidney disease v2.19 COL4A4 Eleanor Williams reviewed gene: COL4A4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31922066; Phenotypes: cystic kidney disease MONDO:0002473; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.19 ALG9 Arina Puzriakova Classified gene: ALG9 as Amber List (moderate evidence)
Cystic kidney disease v2.19 ALG9 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Cystic kidney disease v2.19 ALG9 Arina Puzriakova Gene: alg9 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.18 ALG9 Arina Puzriakova Tag for-review tag was added to gene: ALG9.
Cystic kidney disease v2.18 ALG8 Arina Puzriakova Classified gene: ALG8 as Amber List (moderate evidence)
Cystic kidney disease v2.18 ALG8 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Cystic kidney disease v2.18 ALG8 Arina Puzriakova Gene: alg8 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.17 ALG8 Arina Puzriakova Tag for-review tag was added to gene: ALG8.
Cystic kidney disease v2.17 COL4A4 John Sayer gene: COL4A4 was added
gene: COL4A4 was added to Cystic kidney disease. Sources: Other
Mode of inheritance for gene: COL4A4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A4 were set to 31922066
Phenotypes for gene: COL4A4 were set to cystic kidney disease
Penetrance for gene: COL4A4 were set to unknown
Review for gene: COL4A4 was set to AMBER
Added comment: may phenocopy PKD1
Sources: Other
Cystic kidney disease v2.17 COL4A5 John Sayer changed review comment from: COLA5 may cause mild cystic kidney disease
Sources: Other; to: COL4A5 may cause mild cystic kidney disease
Sources: Other
Cystic kidney disease v2.17 COL4A5 John Sayer gene: COL4A5 was added
gene: COL4A5 was added to Cystic kidney disease. Sources: Other
Mode of inheritance for gene: COL4A5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: COL4A5 were set to 31922066
Phenotypes for gene: COL4A5 were set to cystic kidney disease
Penetrance for gene: COL4A5 were set to unknown
Review for gene: COL4A5 was set to GREEN
Added comment: COLA5 may cause mild cystic kidney disease
Sources: Other
Cystic kidney disease v2.17 SEC61A1 Rebecca Foulger Phenotypes for gene: SEC61A1 were changed from interstitial nephritis; chronic kidney disease; cystic kidney disease; Hyperuricemic nephropathy, familial juvenile, 4, 617056 to glomerulocystic kidney disease; interstitial nephritis; chronic kidney disease; cystic kidney disease; Hyperuricemic nephropathy, familial juvenile, 4, 617056
Cystic kidney disease v2.16 SEC61A1 Rebecca Foulger Phenotypes for gene: SEC61A1 were changed from interstitial nephritis; chronic kidney disease; cystic kidney disease; ator) Hyperuricemic nephropathy, familial juvenile, 4, 617056 to interstitial nephritis; chronic kidney disease; cystic kidney disease; Hyperuricemic nephropathy, familial juvenile, 4, 617056
Cystic kidney disease v2.15 SEC61A1 Rebecca Foulger Phenotypes for gene: SEC61A1 were changed from interstitial nephritis; chronic kidney disease; cystic kidney disease to interstitial nephritis; chronic kidney disease; cystic kidney disease; ator) Hyperuricemic nephropathy, familial juvenile, 4, 617056
Cystic kidney disease v2.14 SEC61A1 Rebecca Foulger Mode of inheritance for gene: SEC61A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.13 SEC61A1 Rebecca Foulger Classified gene: SEC61A1 as Amber List (moderate evidence)
Cystic kidney disease v2.13 SEC61A1 Rebecca Foulger Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.12 ALG8 Rebecca Foulger Publications for gene: ALG8 were set to 30135240
Cystic kidney disease v2.11 ALG8 Rebecca Foulger Phenotypes for gene: ALG8 were changed from cystic liver disease; cystic kidney disease to cystic liver disease; cystic kidney disease; Polycystic liver disease 3 with or without kidney cysts, 617874
Cystic kidney disease v2.10 ALG8 Rebecca Foulger Mode of inheritance for gene: ALG8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.9 ALG8 Rebecca Foulger Classified gene: ALG8 as Green List (high evidence)
Cystic kidney disease v2.9 ALG8 Rebecca Foulger Gene: alg8 has been classified as Green List (High Evidence).
Cystic kidney disease v2.8 ALG9 Rebecca Foulger Classified gene: ALG9 as Green List (high evidence)
Cystic kidney disease v2.8 ALG9 Rebecca Foulger Gene: alg9 has been classified as Green List (High Evidence).
Cystic kidney disease v2.7 ALG9 Rebecca Foulger Phenotypes for gene: ALG9 were changed from cystic liver disease; cystic kidney disease to cystic liver disease; cystic kidney disease; Gillessen-Kaesbach-Nishimura syndrome, 263210
Cystic kidney disease v2.6 ALG9 Rebecca Foulger Publications for gene: ALG9 were set to 31395617
Cystic kidney disease v2.5 ALG9 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI to match review by Eleanor Williams.
Cystic kidney disease v2.5 ALG9 Rebecca Foulger Mode of inheritance for gene: ALG9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cystic kidney disease v2.3 Sarah Leigh Panel version has been signed off
Cystic kidney disease v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Cystic kidney disease v2.0 ALG8 Eleanor Williams edited their review of gene: ALG8: Changed rating: GREEN; Changed publications: 28375157; Changed phenotypes: Polycystic liver disease 3 with or without kidney cysts, 617874; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.0 ALG8 Eleanor Williams changed review comment from: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.

Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel. ; to: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. The proband with 3-4 kidney cysts has a daughter who shares the ALG8 variants and who has no liver cysts but 8 kidney cysts.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.
Cystic kidney disease v2.0 SEC61A1 Eleanor Williams changed review comment from: Associated with Hyperuricemic nephropathy, familial juvenile, 4, #617056 (AD) in OMIM.

PMID: 27392076 - Bolar et al 2016 - report on two families with Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. The father in family B had multiple bilateral simple cysts throughout the kidney. In both families heterozygous missense variants in SEC61A1 were identified - c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly) -both affecting functionally important and conserved residues in SEC61. Functional studies support the renal function for this gene.

PMID: 31488840- Devuyst et al 2019 - a primer that highlights the different types of ADTKD - no new cases

Summary - 1 case reported with kidney cysts; to: Associated with Hyperuricemic nephropathy, familial juvenile, 4, #617056 (AD) in OMIM.

PMID: 27392076 - Bolar et al 2016 - report on two families with Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. The father in family B had multiple bilateral simple cysts throughout the kidney. In both families heterozygous missense variants in SEC61A1 were identified - c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly) -both affecting functionally important and conserved residues in SEC61. Functional studies support the renal function for this gene.

PMID: 31488840- Devuyst et al 2019 - a primer that highlights the different types of ADTKD - no new cases

PMID: 30586318 - Groopman et al 2018 - report 1 case with a heterozygous missense variant in SEC61A1 (p.I428M). The clinical diagnosis was 'Congenital or cystic renal disease' and the genetic diagnosis 'Hyperuricemic nephropathy familial juvenile 4' (See TableS7).

Summary - 2 cases reported with kidney cysts
Cystic kidney disease v2.0 SEC61A1 Eleanor Williams reviewed gene: SEC61A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27392076; Phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, 617056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.0 ALG8 Eleanor Williams changed review comment from: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts. 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.

Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel. ; to: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.

Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel.
Cystic kidney disease v2.0 ALG8 Eleanor Williams changed review comment from: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts. 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.; to: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts. 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.

Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel.
Cystic kidney disease v2.0 ALG9 Eleanor Williams edited their review of gene: ALG9: Changed rating: GREEN; Changed publications: 31395617, 28932688; Changed phenotypes: Gillessen-Kaesbach-Nishimura syndrome, 263210; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cystic kidney disease v2.0 ALG9 Eleanor Williams changed review comment from: Associated with Gillessen-Kaesbach-Nishimura syndrome, 263210 (AR) in OMIM in which Polycystic kidneys is listed as a clinical feature.

PMID: 31395617 - Besse et al 2019 - report 2 patients in a clinically defined cohort with genetically unresolved polycystic liver and kidney disease that had rare heterozygous loss-of-function variants in ALG9. Then using a novel ‘genotype-first’ approach to find ALG9 mutation carriers from a large cohort of exome-sequenced individuals, they found that 7/8 (88%) of ALG9 mutation carriers over age 50 had a least 4 kidney cysts (abstract only accessed).

PMID: 28932688 - Davis et al 2017 - report the case of a proband with ALG9-CDG who has a milder phenotype. This female child was born to non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. A homozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) was identified. Both parents were found to carry one copy of the mutation. In a table of phenotypic features from the 11 known patients with ALG9-CDG (including the one here), 3 other patients are reported with polycystic kidneys and homozygous ALG variants.; to: Associated with Gillessen-Kaesbach-Nishimura syndrome, 263210 (AR) in OMIM in which Polycystic kidneys is listed as a clinical feature.

PMID: 31395617 - Besse et al 2019 - report 2 patients in a clinically defined cohort with genetically unresolved polycystic liver and kidney disease that had rare heterozygous loss-of-function variants in ALG9. Then using a novel ‘genotype-first’ approach to find ALG9 mutation carriers from a large cohort of exome-sequenced individuals, they found that 7/8 (88%) of ALG9 mutation carriers over age 50 had a least 4 kidney cysts (abstract only accessed).

PMID: 28932688 - Davis et al 2017 - report the case of a proband with ALG9-CDG who has a milder phenotype. This female child was born to non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. A homozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) was identified. Both parents were found to carry one copy of the mutation. In a table of phenotypic features from the 11 known patients with ALG9-CDG (including the one here), 3 other patients are reported with polycystic kidneys and homozygous ALG variants.
Cystic kidney disease v2.0 ALG9 Eleanor Williams commented on gene: ALG9
Cystic kidney disease v2.0 ALG8 Eleanor Williams commented on gene: ALG8
Cystic kidney disease v2.0 SEC61A1 John Sayer edited their review of gene: SEC61A1: Changed phenotypes: interstitial nephritis, chronic kidney disease, cystic kidney disease, anaemia, glomerulocystic kidney disease
Cystic kidney disease v2.0 SEC61A1 John Sayer gene: SEC61A1 was added
gene: SEC61A1 was added to Cystic kidney disease. Sources: Expert Review
Mode of inheritance for gene: SEC61A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61A1 were set to 31488840; 27392076
Phenotypes for gene: SEC61A1 were set to interstitial nephritis; chronic kidney disease; cystic kidney disease
Review for gene: SEC61A1 was set to GREEN
Added comment: Sources: Expert Review
Cystic kidney disease v2.0 ALG9 John Sayer gene: ALG9 was added
gene: ALG9 was added to Cystic kidney disease. Sources: Expert Review
Mode of inheritance for gene: ALG9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG9 were set to 31395617
Phenotypes for gene: ALG9 were set to cystic liver disease; cystic kidney disease
Penetrance for gene: ALG9 were set to Complete
Review for gene: ALG9 was set to GREEN
Added comment: Sources: Expert Review
Cystic kidney disease v2.0 ALG8 John Sayer gene: ALG8 was added
gene: ALG8 was added to Cystic kidney disease. Sources: Expert Review
Mode of inheritance for gene: ALG8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG8 were set to 30135240
Phenotypes for gene: ALG8 were set to cystic liver disease; cystic kidney disease
Penetrance for gene: ALG8 were set to Complete
Review for gene: ALG8 was set to GREEN
Added comment: Sources: Expert Review
Cystic kidney disease v2.0 Eleanor Williams promoted panel to version 2.0
Cystic kidney disease v1.49 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Cystic kidney disease v1.48 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Cystic kidney disease v1.47 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 20558538; 22034641
Cystic kidney disease v1.44 WDR19 Eleanor Williams Phenotypes for gene: WDR19 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 13, Senior-Loken
Cystic kidney disease v1.43 WDR19 Eleanor Williams Publications for gene: WDR19 were set to
Cystic kidney disease v1.42 WDR19 Eleanor Williams Mode of inheritance for gene: WDR19 was changed from to BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v1.41 CEP83 Eleanor Williams Classified gene: CEP83 as Green List (high evidence)
Cystic kidney disease v1.41 CEP83 Eleanor Williams Added comment: Comment on list classification: Sufficient cases
Cystic kidney disease v1.41 CEP83 Eleanor Williams Gene: cep83 has been classified as Green List (High Evidence).
Cystic kidney disease v1.40 MAPKBP1 Eleanor Williams Classified gene: MAPKBP1 as Green List (high evidence)
Cystic kidney disease v1.40 MAPKBP1 Eleanor Williams Added comment: Comment on list classification: Sufficient cases
Cystic kidney disease v1.40 MAPKBP1 Eleanor Williams Gene: mapkbp1 has been classified as Green List (High Evidence).
Cystic kidney disease v1.39 WDR19 Anna de Burca Classified gene: WDR19 as Green List (high evidence)
Cystic kidney disease v1.39 WDR19 Anna de Burca Added comment: Comment on list classification: Promoted to green following further discussion with Ellen Thomas. Although this gene is associated with a syndromic presentation, it is appropriate for inclusion in this panel due to the renal element of the phenotype.
Cystic kidney disease v1.39 WDR19 Anna de Burca Gene: wdr19 has been classified as Green List (High Evidence).
Cystic kidney disease v1.38 MAPKBP1 Anna de Burca gene: MAPKBP1 was added
gene: MAPKBP1 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: MAPKBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPKBP1 were set to 28089251
Phenotypes for gene: MAPKBP1 were set to NEPHRONOPHTHISIS 20
Review for gene: MAPKBP1 was set to GREEN
Added comment: PMID:28089251 reports seven variants present in biallelic form in 8 individuals from 5 families. All individuals had nephronophthisis with progression to ESRF in teens to 20s in 5/8 cases.
Sources: Expert list
Cystic kidney disease v1.37 CEP83 Anna de Burca gene: CEP83 was added
gene: CEP83 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: CEP83 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP83 were set to 24882706
Phenotypes for gene: CEP83 were set to NEPHRONOPHTHISIS 18
Review for gene: CEP83 was set to GREEN
Added comment: PMID: 24882706 reports ten variants found in biallelic form in seven families. All but one of the probands had nephronophthisis progressing to end stage renal failure; some of the affected individuals had additional features including intellectual disability and hydrocephalus.
Sources: Expert list
Cystic kidney disease v1.36 DZIP1L Eleanor Williams Phenotypes for gene: DZIP1L were changed from ARPKD; Polycystic kidney disease 5 617610 to ARPKD; Polycystic kidney disease 5 617610
Cystic kidney disease v1.35 PKD2 Eleanor Williams Publications for gene: PKD2 were set to
Cystic kidney disease v1.34 DNAJB11 Eleanor Williams Phenotypes for gene: DNAJB11 were changed from cystic kidney disease; end stage renal failure; non-enlarged kidney to cystic kidney disease; end stage renal failure; non-enlarged kidney; Polycystic kidney disease; Tubulointerstitial kidney disease
Cystic kidney disease v1.33 PKD2 Miranda Durkie edited their review of gene: PKD2: Added comment: Approximately 15% of cases of ADPKD due to mutations in this gene. Majority of mutations are truncating. PKD2 mutation is associated with significantly delayed onset of ESRD relative to PKD1 truncating mutations therefore has important therapeutic and prognostic implications; Changed publications: PMID: 28356211, 23431072 (and many more); Changed phenotypes: Polycystic kidney disease; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v1.33 DNAJB11 Miranda Durkie reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29706351; Phenotypes: Polycystic kidney disease, Tubulointerstitial kidney disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Cystic kidney disease v1.33 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel
Cystic kidney disease v1.32 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease
Cystic kidney disease v1.30 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Cystic kidney disease v1.29 ISCA-37432-Loss Louise Daugherty Region: ISCA-37432-Loss was added
Region: ISCA-37432-Loss was added to Cystic kidney disease. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37432-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37432-Loss were set to RCAD syndrome; utero-vaginal atresia; Schizophrenia; 614527; delayed development, intellectual disability; Renal cysts and diabetes syndrome; Autism Spectrum Disorder; Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females; Chromosome 17q12 deletion syndrome; global developmental delay
Cystic kidney disease v1.29 ISCA-37405-Loss Louise Daugherty Region: ISCA-37405-Loss was added
Region: ISCA-37405-Loss was added to Cystic kidney disease. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37405-Loss was set to BIALLELIC, autosomal or pseudoautosomal
Publications for Region: ISCA-37405-Loss were set to 9856524; 15138899; 8852662
Phenotypes for Region: ISCA-37405-Loss were set to juvenile nephronophthisis 1: including growth retardation. Joubert syndrome: multisystem disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (resulting in the 'molar tooth sign,' or MTS, on axial MRI), mental retardation, hypotonia, irregular breathing pattern, and eye movement abnormalities; 266900; 609583
Cystic kidney disease DNAJB11 Ellen McDonagh classified DNAJB11 as Green List (high evidence)
Cystic kidney disease DNAJB11 Ellen McDonagh classified DNAJB11 as Amber List (moderate evidence)
Cystic kidney disease DNAJB11 John Sayer Added gene to panel
Cystic kidney disease C5orf42 Louise Daugherty commented on C5orf42
Cystic kidney disease CEP290 Ellen McDonagh classified CEP290 as Amber List (moderate evidence)
Cystic kidney disease DZIP1L Ellen McDonagh classified DZIP1L as Green List (high evidence)
Cystic kidney disease DZIP1L John Sayer added DZIP1L to panel
Cystic kidney disease DZIP1L John Sayer reviewed DZIP1L
Cystic kidney disease COL4A1 Ellen McDonagh classified COL4A1 as green
Cystic kidney disease COL4A1 Ellen McDonagh classified COL4A1 as green
Cystic kidney disease COL4A1 Ellen McDonagh classified COL4A1 as green
Cystic kidney disease GANAB Ellen McDonagh classified GANAB as green
Cystic kidney disease GANAB Ellen McDonagh commented on GANAB
Cystic kidney disease GANAB Ellen McDonagh classified GANAB as amber
Cystic kidney disease COL4A1 Ellen McDonagh classified COL4A1 as amber
Cystic kidney disease COL4A1 Ellen McDonagh commented on COL4A1
Cystic kidney disease PKD1 Ellen McDonagh reviewed PKD1
Cystic kidney disease GANAB Miranda Durkie reviewed GANAB
Cystic kidney disease COL4A1 John Sayer added COL4A1 to panel
Cystic kidney disease COL4A1 John Sayer reviewed COL4A1
Cystic kidney disease GANAB John Sayer added GANAB to panel
Cystic kidney disease GANAB John Sayer reviewed GANAB
Cystic kidney disease CEP290 John Sayer reviewed CEP290