Eleanor Williams Added comment: Comment on list classification: Following expert review that some of the reported variants in this gene are relatively common in gnomAD and therefore unlikely to associated with a Mendelian disease, downgrading this gene from amber to red.
Zornitza Stark edited their review of gene: CHD1L: Added comment: Re-evaluation in light of population data: the 6 missense variants reported in the two papers (PMID: 22146311, 24429398) are very common in gnomAD: CHD1L:c.2098G>A; p.Gly700Arg - 1110 hets, 5 hom CHD1L:c.2295A>G; p.Ile765Met - 468 hets, 1 hom CHD1L:c.2479A>G; p.Ile827Val – 725 hets, 2 hom CHD1L:c.998C>G; p.Pro333Arg – 1 het, 0 hom CHD1L:c.1199A>G; p.Glu400Gly – 3 hets, 0 hom CHD1L:c.1551A>G; p.Ile517Met – 195 hets, 0 hom I could not find any other papers for this gene in association with CAKUT. ClinVar only has 1 frameshift variant reported as pathogenic from research in 2001 for an unrelated condition (short stature), the other variants reported in this gene are VUS or LB/B. These population variant frequencies are out of keeping for a Mendelian disorder.; Changed rating: RED; Changed publications: 22146311, 24429398
Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. Although there are 8 families with CAKUT and CHD1L variants, all variants are missense, and there is limited family data available for the patients in PMID:22146311. Also in PMID:22146311, only 2/3 variants were absent from controls, Patient 2 variant was inherited from an asymptomatic mother, and the variant in Patient 3 is predicted benign.
Rebecca Foulger commented on gene: CHD1L: PMID:32164334 show CNVs in genes including CHD1L in 6 CAKUT patients. One patient with bilateral renal cortical cysts and renal stones (ID 41) had a duplication of 1q21.1 encompassing CHD1L.
Rebecca Foulger changed review comment from: PMID:24429398 detected heterozygous variants in CHD1L in 5 families with CAKUT (p.P333R in 1 family, p.E400G in 1 family, p.I517M in 3 Indian families).; to: PMID:24429398 (2014) detected heterozygous variants in CHD1L in 5 families with CAKUT (p.P333R in 1 family, p.E400G in 1 family, p.I517M in 3 Indian families).
Rebecca Foulger commented on gene: CHD1L: PMID:24429398 detected heterozygous variants in CHD1L in 5 families with CAKUT (p.P333R in 1 family, p.E400G in 1 family, p.I517M in 3 Indian families).
Zornitza Stark reviewed gene: CHD1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted