PanelApp

Activity

Filter

Cancel
Date Panel Item Activity
226 actions
Renal Macrocystic Disease v0.85 UGGT1 Krithika Murali Classified gene: UGGT1 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.85 UGGT1 Krithika Murali Gene: uggt1 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.85 UGGT1 Krithika Murali Marked gene: UGGT1 as ready
Renal Macrocystic Disease v0.85 UGGT1 Krithika Murali Gene: uggt1 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.85 UGGT1 Krithika Murali Classified gene: UGGT1 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.85 UGGT1 Krithika Murali Gene: uggt1 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.84 UGGT1 Krithika Murali gene: UGGT1 was added
gene: UGGT1 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGGT1 were set to PMID:40267907
Phenotypes for gene: UGGT1 were set to Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG
Review for gene: UGGT1 was set to AMBER
Added comment: PMID: 40267907 Dardas et al 2025 report 15 affected individuals from 10 unrelated families with biallelic UGGT1 variants and CDG/multisystem disorder with clinical features including GDD/ID,
microcephaly, seizures, craniofacial dysmorphism, and behavioral abnormalities (autism, ADHD). More variable features included congenital heart disease, cryptorchism; recurrent infections; and skeletal anomalies (scoliosis and/or vertebral anomalies).Supportive functional evidence also provided.

Of note, two individuals reported with cystic renal dysplasia and hepatobiliary anomalies that were similar in apperaance to ARPKD.
Sources: Literature
Renal Macrocystic Disease v0.83 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Cystic Kidney Disease, MONDO# 0002473 to {Polycystic kidney disease 9, susceptibility to} MIM#621164
Renal Macrocystic Disease v0.82 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: {Polycystic kidney disease 9, susceptibility to} MIM#621164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.82 COL4A5 Zornitza Stark Classified gene: COL4A5 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.82 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.81 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: AMBER; Mode of pathogenicity: None; 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)
Renal Macrocystic Disease v0.81 COL4A4 Zornitza Stark Classified gene: COL4A4 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.81 COL4A4 Zornitza Stark Gene: col4a4 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.80 COL4A4 Zornitza Stark reviewed gene: COL4A4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.80 COL4A3 Zornitza Stark Classified gene: COL4A3 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.80 COL4A3 Zornitza Stark Gene: col4a3 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.79 COL4A3 Zornitza Stark reviewed gene: COL4A3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome MONDO:0018965; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.79 CFAP47 Chirag Patel changed review comment from: 3 individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts or any family history of cystic kidney disease.

WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased.

CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Sources: Literature; to: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease.

WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased.

CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Sources: Literature
Renal Macrocystic Disease v0.79 CFAP47 Chirag Patel Classified gene: CFAP47 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.79 CFAP47 Chirag Patel Gene: cfap47 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.78 CFAP47 Chirag Patel gene: CFAP47 was added
gene: CFAP47 was added to Renal Macrocystic 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: 39698362
Phenotypes for gene: CFAP47 were set to Cystic kidney disease MONDO:0002473
Review for gene: CFAP47 was set to AMBER
Added comment: 3 individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts or any family history of cystic kidney disease.

WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased.

CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Sources: Literature
Renal Macrocystic Disease v0.77 PKHD1 Bryony Thompson Added comment: Comment on mode of inheritance: Biallelic is Green and Monoallelic is Amber
Renal Macrocystic Disease v0.77 PKHD1 Bryony Thompson Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal Macrocystic Disease v0.76 PKHD1 Bryony Thompson edited their review of gene: PKHD1: Changed publications: 39190485, 21945273
Renal Macrocystic Disease v0.76 PKHD1 Bryony Thompson changed review comment from: Emerging evidence of a monoallelic association with polycystic kidney with/without liver cysts. Enrichment of monoallelic PKHD1 LoF variants (P = 2.98e-08, OR 4.07, 95%CI 2.24-6.88) in 100K GP cystic kidney disease cohort. 50 cases, of which 22 were solved (3 ARPKD & 19 PKD1/2), 2 were partially solved (likely ARPKD), 24 were unsolved (4 with predicted deleterious missense in PKD1/2), and 2 were unascertainable.
18/1209 - with only monoallelic PKHD1 as plausible cause. Enrichment in unexplained (n=266) CyKD cases (P = 5.85e-6, OR 2.92, 95% CI 1.69-4.76).
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).; to: Emerging evidence of a monoallelic association with polycystic kidney with/without liver cysts.
PMID: 39190485 - Enrichment of monoallelic PKHD1 LoF variants (P = 2.98e-08, OR 4.07, 95%CI 2.24-6.88) in 100K GP cystic kidney disease cohort. 50 cases, of which 22 were solved (3 ARPKD & 19 PKD1/2), 2 were partially solved (likely ARPKD), 24 were unsolved (4 with predicted deleterious missense in PKD1/2), and 2 were unascertainable.
18/1209 - with only monoallelic PKHD1 as plausible cause. Enrichment in unexplained (n=266) CyKD cases (P = 5.85e-6, OR 2.92, 95% CI 1.69-4.76).
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
PMID: 21945273 - study suggests carrier status for ARPKD is a predisposition to polycystic liver disease and renal involvement. Ultrasound evaluations on 110 parents from 64 independent ARPKD families (85 molecularly confirmed) identified increased medullary echogenicity in 6 (5.5%) and multiple small liver cysts in 10 parents (9%). Ages of the group ranged from 27 to 66 years (39.5 ± 6.8).
Renal Macrocystic Disease v0.76 PKHD1 Bryony Thompson reviewed gene: PKHD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39190485; Phenotypes: Polycystic kidney disease MONDO:0020642; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Marked gene: COL4A5 as ready
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Gene: col4a5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Classified gene: COL4A5 as Green List (high evidence)
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Gene: col4a5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.75 COL4A5 Bryony Thompson gene: COL4A5 was added
gene: COL4A5 was added to Renal Macrocystic Disease. Sources: Literature
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 38790225; 38680391; 38514012
Phenotypes for gene: COL4A5 were set to Alport syndrome MONDO:0018965
Review for gene: COL4A5 was set to GREEN
gene: COL4A5 was marked as current diagnostic
Added comment: Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels. Also, other studies reporting COL4A5 variants in individuals with a cystic kidney disease phenotype.
Sources: Literature
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Marked gene: COL4A4 as ready
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Gene: col4a4 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Classified gene: COL4A4 as Green List (high evidence)
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Gene: col4a4 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.73 COL4A4 Bryony Thompson gene: COL4A4 was added
gene: COL4A4 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: COL4A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A4 were set to 38514012
Phenotypes for gene: COL4A4 were set to Alport syndrome MONDO:0018965
Review for gene: COL4A4 was set to GREEN
gene: COL4A4 was marked as current diagnostic
Added comment: Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels.
Sources: Literature
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson changed review comment from: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5). A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002).

PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11).
15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
Sources: Literature; to: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels.

PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11).
15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
Sources: Literature
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Marked gene: COL4A3 as ready
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Gene: col4a3 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Classified gene: COL4A3 as Green List (high evidence)
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Gene: col4a3 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.71 COL4A3 Bryony Thompson gene: COL4A3 was added
gene: COL4A3 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: COL4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3 were set to 39190485; 38514012
Phenotypes for gene: COL4A3 were set to Alport syndrome MONDO:0018965
Review for gene: COL4A3 was set to GREEN
gene: COL4A3 was marked as current diagnostic
Added comment: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5). A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002).

PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11).
15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
Sources: Literature
Renal Macrocystic Disease v0.70 ALG8 Chirag Patel edited their review of gene: ALG8: Added comment: 2023 Paper:
236 individuals identified with ALG8 protein-truncating variants. Patients were significantly at increased risk of having any kidney/liver cyst diagnosis (Odds Ratio 2.42), cystic kidney disease (OR 3.03), and nephrolithiasis (OR 1.89). ALG8 PTV heterozygotes were significantly more likely to have cystic kidney disease, defined as four or more kidney cysts (57.7% vs. 7.7%), or bilateral kidney cysts (69.2% vs. 15.4%), but not one or more liver cyst (11.5% vs. 7.7%).

ALG8 PTVs were not associated with chronic kidney disease or kidney failure in the MyCode study or the UK Biobank data. Thus, PTVs in ALG8 result in increased risk of a mild cystic kidney disease phenotype.; Changed publications: PMID: 36574950
Renal Macrocystic Disease v0.70 IFT140 Chirag Patel edited their review of gene: IFT140: Added comment: 368 patients with IFT140 LoF variants and a spectrum of phenotypic findings that support the association of IFT140 with PKD. A cystic phenotype was reported in 223 of the 368 (60.6%) individuals harboring an IFT140 LoF variant, 98% of which had no other identified cause for their cystic disease. Of 122 unique LoF IFT140 variants identified, 56 (46%) were frameshift, 38 (31%) nonsense, 22 (18%) splice site and 6 (5%) exon-level deletions. Only six IFT140 individuals were reported with end-stage kidney disease, consistent with observed milder clinical presentations in IFT140-related PKD.; Changed publications: PMID: 39136524; Changed phenotypes: Cystic Kidney Disease, MONDO# 0002473; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Set current diagnostic: yes
Renal Macrocystic Disease v0.70 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Polycystic kidney disease 8, MIM# 620903
Renal Macrocystic Disease v0.69 NEK8 Zornitza Stark reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 8, MIM# 620903; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.69 ALG9 Ain Roesley Phenotypes for gene: ALG9 were changed from Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease to Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease; ALG9-associated autosomal dominant polycystic kidney disease MONDO:0700000
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Classified gene: NEK8 as Green List (high evidence)
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Gene: nek8 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.67 NEK8 Elena Savva Publications for gene: NEK8 were set to Unpublished ESHG presentation
Renal Macrocystic Disease v0.66 NEK8 Lauren Rogers reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37598857; Phenotypes: Familial cystic renal disease MONDO:0019741; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.66 Zornitza Stark HPO terms changed from to Renal cyst, HP:0000107
List of related panels changed from to Renal cyst; HP:0000107
Renal Macrocystic Disease v0.63 LRP5 Zornitza Stark edited their review of gene: LRP5: Added comment: ClinGen assessment is LIMITED (2020).; Changed phenotypes: Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Renal Macrocystic Disease v0.63 SEC16B Zornitza Stark Marked gene: SEC16B as ready
Renal Macrocystic Disease v0.63 SEC16B Zornitza Stark Gene: sec16b has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.63 SEC16B Zornitza Stark Phenotypes for gene: SEC16B were changed from Polycystic liver disease with or without renal cysts, no OMIM # to Polycystic liver disease (with or without kidney cysts), MONDO:0000447, SEC16B-related
Renal Macrocystic Disease v0.62 SEC16B Zornitza Stark Classified gene: SEC16B as Amber List (moderate evidence)
Renal Macrocystic Disease v0.62 SEC16B Zornitza Stark Gene: sec16b has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.61 SEC16B Zornitza Stark reviewed gene: SEC16B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic liver disease (with or without kidney cysts), MONDO:0000447, SEC16B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.61 ALG8 Zornitza Stark Marked gene: ALG8 as ready
Renal Macrocystic Disease v0.61 ALG8 Zornitza Stark Gene: alg8 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.60 LRP5 Chirag Patel reviewed gene: LRP5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal Macrocystic Disease v0.60 SEC63 Chirag Patel Classified gene: SEC63 as Green List (high evidence)
Renal Macrocystic Disease v0.60 SEC63 Chirag Patel Gene: sec63 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.59 SEC63 Chirag Patel edited their review of gene: SEC63: Added comment: CLINGEN assessed as DEFINITIVE (2020)

SEC63 was FIRST reported in relation to autosomal dominant polycystic liver disease (ADPLD) in 2004 (Davila et al., PMID 15133510). ADPLD due to SEC63 mutations (ADPLD-SEC63) is diagnosed in adults with a family history of liver cysts, under age 40 with any number of liver cysts and individuals over the age of 40 with four or more liver cysts. Women are associated with more severe course of disease, and kidney cysts are present in approximately 28-35% of cases, but in these cases the kidney disease is mild with no association with progression to end stage renal disease (PMID 20408995). At least twenty unique variants (e.g. nonsense, frameshift, splice site, missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, population data and experimental data. Summary of Case Level Data: 12 POINTS. Variants in this gene have been reported in at least 19 probands and in at least four publications (PMID 15133510, PMID 16835903, PMID 20095989, PMID 28375157). Variants in this gene segregated with disease in at least 24 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is heterozygous loss of function (PMID 15133510, PMID 20095989), with experimental evidence suggesting endoplasmic reticulum stress with induction of the unfolded protein response (UPR) and association with aberrant polycystin 1 (PC1) post-translational modifications leading to cystogenesis (PMID 22864019, PMID 25844898). This gene-disease association is supported by expression studies in cell models, zebrafish models, and mouse models (PMID 21685914, PMID 22864019, PMID 25844898). In summary, SEC63 is definitively associated with AUTOSOMAL DOMINANT POLYCYSTIC LIVER DISEASE. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.; Changed rating: GREEN
Renal Macrocystic Disease v0.59 PRKCSH Chirag Patel Classified gene: PRKCSH as Green List (high evidence)
Renal Macrocystic Disease v0.59 PRKCSH Chirag Patel Gene: prkcsh has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.58 PRKCSH Chirag Patel reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal Macrocystic Disease v0.58 ALG8 Chirag Patel Classified gene: ALG8 as Green List (high evidence)
Renal Macrocystic Disease v0.58 ALG8 Chirag Patel Gene: alg8 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.57 ALG8 Chirag Patel Deleted their comment
Renal Macrocystic Disease v0.57 ALG8 Chirag Patel edited their review of gene: ALG8: Added comment: Based on similar ALG genes, the CLINGEN review is discrepant to their review on other similar ALG genes with similar genetic and experimental evidence. Given patients present with PLD with kidney cysts, decision made that evidence is sufficient for PanelApp for classification as GREEN.

CLINGEN assessed as LIMITED (2020)
Monoallelic ALG8 pathogenic variants were first reported in relation to autosomal dominant polycystic liver disease (ADPLD) in 2017 (Besse et al., PMID: 28375157). Of note, biallelic ALG8 pathogenic variants have been associated with congenital disorder of glycosylation, type Ih (CDG-1h; OMIM #608104). Given that ALG8-associated ADPLD and ALG8-associated CDG-1h have different inheritance modes and phenotypic manifestations, we have split the two disease entities. As noted above, here we only curate the association between ALG8 and ADPLD. At least 3 variants (2 nonsense, 1 splice) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, population-level data, and experimental data. Variants in this gene have been reported in at least 6 probands in 2 publications (PMID: 28375157; PMID: 32457805). This gene-disease association is supported by in vitro functional assays showing reduced maturation of polycystin 1 in ALG8 null cells. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.; Changed rating: GREEN
Renal Macrocystic Disease v0.57 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; KidGen; Rare Disease; Royal Melbourne Hospital; Genetic Health Queensland
Renal Macrocystic Disease v0.56 ALG9 Chirag Patel Classified gene: ALG9 as Green List (high evidence)
Renal Macrocystic Disease v0.56 ALG9 Chirag Patel Gene: alg9 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.55 ALG9 Chirag Patel reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31395617, 32398770; Phenotypes: Polycystic kidney disease; Mode of inheritance: None
Renal Macrocystic Disease v0.55 SEC16B Chirag Patel gene: SEC16B was added
gene: SEC16B was added to Renal Macrocystic Disease. Sources: Expert Review
Mode of inheritance for gene: SEC16B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC16B were set to PMID: 28375157, 28862642, 30652979
Phenotypes for gene: SEC16B were set to Polycystic liver disease with or without renal cysts, no OMIM #
Review for gene: SEC16B was set to RED
Added comment: CLINGEN assessed as LIMITED (2020)
No further evidence since for kidney cysts

SEC61B was first reported in relation to autosomal dominant polycystic liver disease in 2017 (Besse et al., PMID:28375157). At least 2 variants (frameshift, start-loss) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 2 probands in 1 publication (PMID:28375157). This gene-disease association is supported by in vitro functional assays. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
Sources: Expert Review
Renal Macrocystic Disease v0.54 ALG8 Chirag Patel gene: ALG8 was added
gene: ALG8 was added to Renal Macrocystic 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 PMID: 28375157, 32457805
Phenotypes for gene: ALG8 were set to Polycystic liver disease 3 with or without kidney cysts, MIM# 617874
Review for gene: ALG8 was set to RED
Added comment: CLINGEN assessed as LIMITED (2020)
No further evidence since then for kidney cysts.

Monoallelic ALG8 pathogenic variants were first reported in relation to autosomal dominant polycystic liver disease (ADPLD) in 2017 (Besse et al., PMID: 28375157). Of note, biallelic ALG8 pathogenic variants have been associated with congenital disorder of glycosylation, type Ih (CDG-1h; OMIM #608104). Given that ALG8-associated ADPLD and ALG8-associated CDG-1h have different inheritance modes and phenotypic manifestations, we have split the two disease entities. As noted above, here we only curate the association between ALG8 and ADPLD. At least 3 variants (2 nonsense, 1 splice) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, population-level data, and experimental data. Variants in this gene have been reported in at least 6 probands in 2 publications (PMID: 28375157; PMID: 32457805). This gene-disease association is supported by in vitro functional assays showing reduced maturation of polycystin 1 in ALG8 null cells. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
Sources: Expert Review
Renal Macrocystic Disease v0.53 ALG5 Zornitza Stark reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 7, MIM# 620056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.53 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Cystic renal disease MONDO:0002473, ALG5-related; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline to Polycystic kidney disease 7, MIM# 620056; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Renal Macrocystic Disease v0.52 IFT140 Chirag Patel reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline to Cystic renal disease MONDO:0002473, ALG5-related; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Renal Macrocystic Disease v0.51 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Renal Macrocystic Disease v0.51 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.50 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Renal Macrocystic Disease v0.50 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Publications for gene: PMM2 were set to PMID: 28373276, 32595772
Renal Macrocystic Disease v0.49 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD) to Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Renal Macrocystic Disease v0.48 PMM2 Zornitza Stark Tag 5'UTR tag was added to gene: PMM2.
Renal Macrocystic Disease v0.48 PMM2 Chirag Patel Classified gene: PMM2 as Green List (high evidence)
Renal Macrocystic Disease v0.48 PMM2 Chirag Patel Gene: pmm2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.47 PMM2 Chirag Patel gene: PMM2 was added
gene: PMM2 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to PMID: 28373276, 32595772
Phenotypes for gene: PMM2 were set to Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD)
Review for gene: PMM2 was set to GREEN
gene: PMM2 was marked as current diagnostic
Added comment: Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts.

Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD.

None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.
Sources: Literature
Renal Macrocystic Disease v0.46 NEK8 Zornitza Stark Marked gene: NEK8 as ready
Renal Macrocystic Disease v0.46 NEK8 Zornitza Stark Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.46 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal cystic disease to Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Renal Macrocystic Disease v0.45 NEK8 Chirag Patel Classified gene: NEK8 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.45 NEK8 Chirag Patel Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Classified gene: NEK8 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Classified gene: NEK8 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.43 NEK8 Chirag Patel gene: NEK8 was added
gene: NEK8 was added to Renal Macrocystic Disease. Sources: Other
Mode of inheritance for gene: NEK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEK8 were set to Unpublished ESHG presentation
Phenotypes for gene: NEK8 were set to Renal cystic disease
Mode of pathogenicity for gene: NEK8 was set to Other
Review for gene: NEK8 was set to AMBER
Added comment: 12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs)
-3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln)
-suspected dominant negative effect
-patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8
(Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF)
Sources: Other
Renal Macrocystic Disease v0.42 DZIP1L Yu Leng Phua Deleted their review
Renal Macrocystic Disease v0.42 DZIP1L Yu Leng Phua Deleted their comment
Renal Macrocystic Disease v0.42 DZIP1L Yu Leng Phua reviewed gene: DZIP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 35211789; Phenotypes: Polycystic kidney disease 5, MIM#617610; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.42 IFT140 Alison Yeung Marked gene: IFT140 as ready
Renal Macrocystic Disease v0.42 IFT140 Alison Yeung Gene: ift140 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.42 IFT140 Alison Yeung Classified gene: IFT140 as Green List (high evidence)
Renal Macrocystic Disease v0.42 IFT140 Alison Yeung Gene: ift140 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.41 IFT140 Alison Yeung gene: IFT140 was added
gene: IFT140 was added to Renal Macrocystic Disease. Sources: Literature
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, MONDO# 0002473
Review for gene: IFT140 was set to GREEN
Added comment: 12 unrelated families reported with monoallelic variants causing mild polycystic kidney disease with large cysts, limited kidney insufficiency, and few liver cysts.
Sources: Literature
Renal Macrocystic Disease v0.40 DNAJB11 Zornitza Stark Phenotypes for gene: DNAJB11 were changed from Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061 to Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061; Ivermark II syndrome.
Renal Macrocystic Disease v0.39 DNAJB11 Zornitza Stark Publications for gene: DNAJB11 were set to 29706351; 29777155
Renal Macrocystic Disease v0.38 DNAJB11 Zornitza Stark Mode of inheritance for gene: DNAJB11 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
Renal Macrocystic Disease v0.37 DNAJB11 Zornitza Stark changed review comment from: Single family reported with severe, fetal onset renal cystic disease, dilation and proliferation of pancreatic duct cells, and liver ductal plate malformation, an association known as Ivemark II syndrome.; to: Single family reported with bi-allelic variant and severe, fetal onset renal cystic disease, dilation and proliferation of pancreatic duct cells, and liver ductal plate malformation, an association known as Ivemark II syndrome.
Renal Macrocystic Disease v0.37 DNAJB11 Zornitza Stark changed review comment from: Seven families described with phenotypes overlapping ADTKD and ADPKD.
Sources: Expert list; to: Seven families described with phenotypes overlapping ADTKD and ADPKD and mono-allelic variants in this gene.
Sources: Expert list
Renal Macrocystic Disease v0.37 DNAJB11 Zornitza Stark edited their review of gene: DNAJB11: Added comment: Single family reported with severe, fetal onset renal cystic disease, dilation and proliferation of pancreatic duct cells, and liver ductal plate malformation, an association known as Ivemark II syndrome.; Changed publications: 29706351, 29777155, 33129895; Changed phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061, Ivermark II syndrome.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal Macrocystic Disease v0.37 ALG9 Zornitza Stark changed review comment from: Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. Bi-allelic variants cause CDG: kidney cysts reported as part of phenotype but note this is generally a severe multi-system disorder.
Sources: Literature; to: Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. Bi-allelic variants cause CDG: kidney cysts reported as part of phenotype but note this is generally a severe multi-system disorder. It is unclear at present whether the mechanism is the same for both. It may be that bi-allelic LOF is perinatal lethal, hence CDG carriers for missense variants are less likely to manifest renal cysts.
Sources: Literature
Renal Macrocystic Disease v0.37 ALG9 Zornitza Stark edited their review of gene: ALG9: Added comment: Additional individual reported in PMID 30676690 as part of a large cohort.; Changed publications: 31395617, 32398770; Changed phenotypes: Congenital disorder of glycosylation, type Il, MIM# 608776, Gillessen-Kaesbach-Nishimura syndrome, MIM#263210, Polycystic kidney disease
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Marked gene: GANAB as ready
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Gene: ganab has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Phenotypes for gene: GANAB were changed from to Polycystic kidney disease 3, MIM# 600666
Renal Macrocystic Disease v0.36 GANAB Zornitza Stark Publications for gene: GANAB were set to
Renal Macrocystic Disease v0.35 GANAB Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.34 GANAB Zornitza Stark reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259053; Phenotypes: Polycystic kidney disease 3, MIM# 600666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Renal Macrocystic Disease v0.33 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.33 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.32 PKHD1 Zornitza Stark reviewed gene: PKHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark Gene: lrp5 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark gene: LRP5 was added
gene: LRP5 was added to Renal Macrocystic Disease. Sources: Expert list
Mode of inheritance for gene: LRP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRP5 were set to 25920554; 24706814
Phenotypes for gene: LRP5 were set to Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Review for gene: LRP5 was set to RED
Added comment: 5 families reported. However, some non-penetrance reported in family members in original family. In two of the families reported subsequently, PKD1 LP variants were found and LRP5 variant was postulated to be a modifier. Note that one of the variants p.Arg1036Gln is present in 692 individuals in gnomad, p.Trp560Cys is present in 9, and p.Arg1135Cys is present in 70. Overall limited evidence for association with cystic renal phenotype. Note the gene has a well-established association with eye/bone phenotypes.
Sources: Expert list
Renal Macrocystic Disease v0.31 SEC63 Zornitza Stark edited their review of gene: SEC63: Changed rating: RED
Renal Macrocystic Disease v0.31 PRKCSH Zornitza Stark Classified gene: PRKCSH as Amber List (moderate evidence)
Renal Macrocystic Disease v0.31 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.30 PRKCSH Zornitza Stark edited their review of gene: PRKCSH: Changed rating: AMBER
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Marked gene: ALG9 as ready
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Gene: alg9 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Classified gene: ALG9 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Gene: alg9 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.29 ALG9 Zornitza Stark gene: ALG9 was added
gene: ALG9 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: ALG9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALG9 were set to 31395617
Phenotypes for gene: ALG9 were set to Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease
Review for gene: ALG9 was set to AMBER
Added comment: Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. Bi-allelic variants cause CDG: kidney cysts reported as part of phenotype but note this is generally a severe multi-system disorder.
Sources: Literature
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark changed review comment from: Well established gene-disease relationship, >50 reported families.; to: Well established gene-disease relationship, >50 reported families. Liver cystic disease predominates the clinical presentation, generally a small number of kidney cysts.
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from Polycystic liver disease 1, MIM# 174050, with or without kidney cysts to Polycystic liver disease 1, MIM# 174050, with or without kidney cysts
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Marked gene: PRKCSH as ready
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1, MIM# 174050, with or without kidney cysts
Renal Macrocystic Disease v0.27 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Renal Macrocystic Disease v0.26 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.25 PRKCSH Zornitza Stark reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577059; Phenotypes: Polycystic liver disease 1, MIM# 174050, with or without kidney cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.25 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; KidGen; Royal Melbourne Hospital; Rare Disease
Renal Macrocystic Disease v0.24 PKD1 Zornitza Stark Marked gene: PKD1 as ready
Renal Macrocystic Disease v0.24 PKD1 Zornitza Stark Gene: pkd1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.24 PKD1 Zornitza Stark Phenotypes for gene: PKD1 were changed from to Polycystic kidney disease 1, MIM# 173900
Renal Macrocystic Disease v0.23 PKD1 Zornitza Stark Mode of inheritance for gene: PKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.22 PKD1 Chern Lim reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 1, MIM# 173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Renal Macrocystic Disease v0.22 PKD2 Zornitza Stark Phenotypes for gene: PKD2 were changed from Polycystic kidney disease 2, MIM#613095 AD to Polycystic kidney disease 2, MIM#613095 AD
Renal Macrocystic Disease v0.21 PKD2 Zornitza Stark Marked gene: PKD2 as ready
Renal Macrocystic Disease v0.21 PKD2 Zornitza Stark Gene: pkd2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.21 PKD2 Zornitza Stark Phenotypes for gene: PKD2 were changed from to Polycystic kidney disease 2, MIM#613095 AD
Renal Macrocystic Disease v0.20 PKD2 Zornitza Stark Mode of inheritance for gene: PKD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.19 PKD2 Michelle Torres reviewed gene: PKD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11854751; Phenotypes: Polycystic kidney disease 2 (613095 AD); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.19 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; KidGen; Rare Disease
Renal Macrocystic Disease v0.18 Zornitza Stark Panel name changed from Renal macrocystic disease_KidGen_VCGS to Renal Macrocystic Disease
Panel types changed to Victorian Clinical Genetics Services; KidGen
Renal Macrocystic Disease v0.17 VHL Zornitza Stark Marked gene: VHL as ready
Renal Macrocystic Disease v0.17 VHL Zornitza Stark Gene: vhl has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.17 VHL Zornitza Stark Classified gene: VHL as Green List (high evidence)
Renal Macrocystic Disease v0.17 VHL Zornitza Stark Gene: vhl has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.16 VHL Zornitza Stark gene: VHL was added
gene: VHL was added to Renal macrocystic disease_KidGen_VCGS. Sources: Expert list
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: VHL were set to von Hippel-Lindau syndrome, MIM# 193300
Review for gene: VHL was set to GREEN
Added comment: Multiple renal cysts are part of the phenotype.
Sources: Expert list
Renal Macrocystic Disease v0.15 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Renal Macrocystic Disease v0.15 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.15 COL4A1 Zornitza Stark Classified gene: COL4A1 as Green List (high evidence)
Renal Macrocystic Disease v0.15 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.14 COL4A1 Zornitza Stark gene: COL4A1 was added
gene: COL4A1 was added to Renal macrocystic disease_KidGen_VCGS. Sources: Expert list
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 25719457; 15882279
Phenotypes for gene: COL4A1 were set to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM# 611773
Review for gene: COL4A1 was set to GREEN
Added comment: Large renal cysts described in multiple individuals with this condition.
Sources: Expert list
Renal Macrocystic Disease v0.13 SEC63 Chirag Patel changed review comment from: Very few renal cysts seen in patients. If this PLD gene is in the panel, then we should have all the PLD genes, where very occasional renal cysts can be seen.; to: Renal cysts not a key or common feature seen in these patients. If this PLD gene is in the panel, then we should have all the PLD genes, where very occasional renal cysts can be seen.
Renal Macrocystic Disease v0.13 SEC63 Zornitza Stark Classified gene: SEC63 as Red List (low evidence)
Renal Macrocystic Disease v0.13 SEC63 Zornitza Stark Added comment: Comment on list classification: Discussed with Chirag Patel: we should have a consistent approach to all liver cystic disease genes. Renal cysts are not a key feature, therefore Red for this panel.
Renal Macrocystic Disease v0.13 SEC63 Zornitza Stark Gene: sec63 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.12 SEC63 Chirag Patel reviewed gene: SEC63: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic liver disease 2, OMIM #617004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.12 SEC63 Zornitza Stark Marked gene: SEC63 as ready
Renal Macrocystic Disease v0.12 SEC63 Zornitza Stark Gene: sec63 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.12 SEC63 Zornitza Stark Classified gene: SEC63 as Green List (high evidence)
Renal Macrocystic Disease v0.12 SEC63 Zornitza Stark Gene: sec63 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.11 SEC63 Zornitza Stark gene: SEC63 was added
gene: SEC63 was added to Renal macrocystic disease_KidGen_VCGS. Sources: Expert list
Mode of inheritance for gene: SEC63 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC63 were set to 15133510
Phenotypes for gene: SEC63 were set to Polycystic liver disease 2, MIM#617004
Review for gene: SEC63 was set to GREEN
Added comment: Renal cysts reported in some individuals; no significant renal impairment.
Sources: Expert list
Renal Macrocystic Disease v0.10 Chirag Patel Panel name changed from Renal cystic disease_KidGen_VCGS to Renal macrocystic disease_KidGen_VCGS
Renal Macrocystic Disease v0.9 Zornitza Stark removed gene:ALMS1 from the panel
Renal Macrocystic Disease v0.8 Zornitza Stark removed gene:ACTN4 from the panel
Renal Macrocystic Disease v0.7 Zornitza Stark Panel name changed from Renal cystic disease_KidGen to Renal cystic disease_KidGen_VCGS
Renal Macrocystic Disease v0.6 DZIP1L Zornitza Stark Marked gene: DZIP1L as ready
Renal Macrocystic Disease v0.6 DZIP1L Zornitza Stark Gene: dzip1l has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.6 DZIP1L Zornitza Stark Classified gene: DZIP1L as Green List (high evidence)
Renal Macrocystic Disease v0.6 DZIP1L Zornitza Stark Gene: dzip1l has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.5 DZIP1L Zornitza Stark gene: DZIP1L was added
gene: DZIP1L was added to Renal cystic disease_KidGen. Sources: Expert list
Mode of inheritance for gene: DZIP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DZIP1L were set to 28530676
Phenotypes for gene: DZIP1L were set to Polycystic kidney disease 5, MIM#617610
Review for gene: DZIP1L was set to GREEN
gene: DZIP1L was marked as current diagnostic
Added comment: 7 individuals from 4 unrelated families with bi-allelic variants in this gene.
Sources: Expert list
Renal Macrocystic Disease v0.4 DNAJB11 Zornitza Stark Marked gene: DNAJB11 as ready
Renal Macrocystic Disease v0.4 DNAJB11 Zornitza Stark Gene: dnajb11 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.4 DNAJB11 Zornitza Stark Classified gene: DNAJB11 as Green List (high evidence)
Renal Macrocystic Disease v0.4 DNAJB11 Zornitza Stark Gene: dnajb11 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.3 DNAJB11 Zornitza Stark gene: DNAJB11 was added
gene: DNAJB11 was added to Renal cystic disease_KidGen. Sources: Expert list
Mode of inheritance for gene: DNAJB11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNAJB11 were set to 29706351; 29777155
Phenotypes for gene: DNAJB11 were set to Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061
Review for gene: DNAJB11 was set to GREEN
gene: DNAJB11 was marked as current diagnostic
Added comment: Seven families described with phenotypes overlapping ADTKD and ADPKD.
Sources: Expert list
Renal Macrocystic Disease v0.2 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Renal Macrocystic Disease v0.2 ALMS1 Zornitza Stark Gene: alms1 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.2 ALMS1 Zornitza Stark Classified gene: ALMS1 as Red List (low evidence)
Renal Macrocystic Disease v0.2 ALMS1 Zornitza Stark Gene: alms1 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.1 ALMS1 Zornitza Stark reviewed gene: ALMS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal Macrocystic Disease v0.1 ACTN4 Zornitza Stark Marked gene: ACTN4 as ready
Renal Macrocystic Disease v0.1 ACTN4 Zornitza Stark Gene: actn4 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.1 ACTN4 Zornitza Stark Classified gene: ACTN4 as Red List (low evidence)
Renal Macrocystic Disease v0.1 ACTN4 Zornitza Stark Gene: actn4 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.0 ACTN4 Zornitza Stark reviewed gene: ACTN4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal Macrocystic Disease v0.0 ALMS1 Zornitza Stark gene: ALMS1 was added
gene: ALMS1 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: ALMS1 was set to Unknown
Renal Macrocystic Disease v0.0 ACTN4 Zornitza Stark gene: ACTN4 was added
gene: ACTN4 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: ACTN4 was set to Unknown
Renal Macrocystic Disease v0.0 UMOD Zornitza Stark gene: UMOD was added
gene: UMOD was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: UMOD was set to Unknown
Renal Macrocystic Disease v0.0 TSC2 Zornitza Stark gene: TSC2 was added
gene: TSC2 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: TSC2 was set to Unknown
Renal Macrocystic Disease v0.0 TSC1 Zornitza Stark gene: TSC1 was added
gene: TSC1 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: TSC1 was set to Unknown
Renal Macrocystic Disease v0.0 PRKCSH Zornitza Stark gene: PRKCSH was added
gene: PRKCSH was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: PRKCSH was set to Unknown
Renal Macrocystic Disease v0.0 PKHD1 Zornitza Stark gene: PKHD1 was added
gene: PKHD1 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: PKHD1 was set to Unknown
Renal Macrocystic Disease v0.0 PKD2 Zornitza Stark gene: PKD2 was added
gene: PKD2 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: PKD2 was set to Unknown
Renal Macrocystic Disease v0.0 PKD1 Zornitza Stark gene: PKD1 was added
gene: PKD1 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: PKD1 was set to Unknown
Renal Macrocystic Disease v0.0 MUC1 Zornitza Stark gene: MUC1 was added
gene: MUC1 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: MUC1 was set to Unknown
Renal Macrocystic Disease v0.0 HNF1B Zornitza Stark gene: HNF1B was added
gene: HNF1B was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: HNF1B was set to Unknown
Renal Macrocystic Disease v0.0 GANAB Zornitza Stark gene: GANAB was added
gene: GANAB was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green
Mode of inheritance for gene: GANAB was set to Unknown
Renal Macrocystic Disease v0.0 Zornitza Stark Added panel Renal cystic disease_KidGen