Table 1 Rare heterozygous variants in the GDF6 gene predicted to be “deleterious” identified in 3 of 194 patients with renal anomalies.
From: Rare heterozygous GDF6 variants in patients with renal anomalies
Patient, gender, origin | Chromosomal positiona, SNP number | Nucleotide change, amino acid change | MAF according to gnomADb | Predictions | Inheritance | Renal phenotype | Extrarenal phenotype | ClinVar associations | Clinical interpretation and ACMG/AMP codes [23] | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
MutationTaster | SIFT | PolyPhen-2 | |||||||||
N038.II.1, female, Norway (African mother from Ghana, Caucasian father from UK) | 8:97172809, rs139075817 | c.112G>C p.(Gly38Arg) | 0.000656 0.000000 0.007016 | “Polymorphism” | “Damaging” | “Possibly damaging” | Not paternal | Bilateral kidney hypodysplasia requiring kidney transplantation at age 5 years | Features of Klippel–Feil syndrome 1 (i.e., high-arched palate), macrocephaly, short narrow palpebral fissures | Not reported | “Uncertain significance” (PS3_strong; PP2_supporting; PP3_supporting; PP4_supporting) |
F006.II.1, female, Germany | 8:97157413, rs121909352 | c.746C>A p.(Ala249Glu) | 0.001948 0.003783 0.000295 | “Disease causing” | “Tolerated” | “Benign” | Maternal | Left-sided crossed fused renal ectopia with hydronephrosis, megaureters and VUR | Features of Klippel–Feil syndrome 1 (i.e., vertebral segmentation defects including fusions, scoliosis, left-sided auricle dysplasia, and aplasia of the external auditory canal), anal atresia, rectovestibular fistula, small ventricular septal defects, patent foramen ovale, anisometropia, suspected microphthalmia | Klippel–Feil syndrome 1, isolated microphthalmia, Leber congenital amaurosis | “Pathogenic” (PS1_strong; PS3_strong) |
H435.II.1, male, North Macedonia | 8:97157413, rs121909352 | c.746C>A p.(Ala249Glu) | 0.001948 0.003783 0.000295 | “Disease causing” | “Tolerated” | “Benign” | Paternal | Left-sided kidney hypodysplasia, nonfunctional on DMSA scan | Features of Klippel–Feil syndrome 1 (i.e., scoliosis, high-arched palate), lop ears, prognathism, short philtrum, short frenulum | Klippel–Feil syndrome 1, isolated microphthalmia, Leber congenital amaurosis | “Pathogenic” (PS1_strong; PS3_strong) |
