Unexplained young onset end-stage renal disease - additional genes

Gene: BNC2

Green List (high evidence)

This gene has been added to this panel with green rating as it was present in R257 Unexplained young onset end-stage renal disease panel (v5.1) with the same rating before it was made a super panel.

Created: 25 Sep 2024, 9:36 p.m. | Last Modified: 25 Sep 2024, 9:36 p.m.

Panel Version: 0.65

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

I don't know

Gene imported from the 'Renal and urinary tract disorders' panel v1.8 with a rating of Amber

Created: 9 Apr 2019, 11:17 a.m.

Green List (high evidence)

Comment on list classification: Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.

Created: 3 Jun 2019, 10:45 a.m.

Comment on publications: added publication to support upgrading gene to green

Created: 3 Jun 2019, 10:43 a.m.

New publication PMID: 31051115 Kolvenbach CM et al., (2019) supports the rating of this gene from Amber to Green. Though exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.

Created: 3 Jun 2019, 10:30 a.m.

Comment on list classification: New gene added by external reviewer. Changed from Red to Amber and added tag watchlist. Awaiting publication before making gene green.

Created: 9 Oct 2018, 4:04 p.m.

Red List (low evidence)

BNC2 was presented at the European Society of Paediatric Nephrology meeting in October 2018 as a new disease gene causing posterior urethral valves (PUV) by Dr Alina Hilger from Bonn, Germany. It was identified in 3 families affected by PUV. A publication is reportedly submitted.
Sources: Other

Created: 7 Oct 2018, 7:42 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
PUV

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments