Submission Details

Autosomal dominant

07/28/2020

The TCF20 gene is located on chromosome 22 at 22q13.2 and encodes the transcription factor 20 protein. TCF20 regulates gene transcription by acting as a coactivaor for a variety of other transcription factors. TCF20 was first associated with autosomal dominant neurodevelopmental disorders in 2014 (25228304: Babbs et al.2014 ). Evidence supporting this gene-disease relationship includes case-level data and limited experimental data. This curation included seven unique variants (five frameshift and two stop-gained) identified in seven unrelated probands from three publications (25228304: Babbs et al. 2014; 27436265: Schäfgen et al. 2016; 30819258: Vetrini et al. 2019). In the majority of reported cases, variants occurred de novo, but rare cases of a variant inherited from an affected parent have been reported. Notably, two independent evaluations demonstrated that the truncated transcripts escape from nonsense-mediated decay. More genetic evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. Haploinsufficiency has been suggested as the mechanism for disease. This gene-disease relationship is also supported by expression in the brain and a shared biochemical function with another gene associated with a similar phenotype (RAI1) (30819258: Vetrini et al. 2019). In summary, there is strong evidence to support the relationship between TCF20 and autosomal dominant TCF20-associated neurodevelopmental disorders. Additional experimental evidence is needed to reach a definitive classification.

25228304 27436265 30819258 25613900