ClinVar

Description

The A209G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, different amino acid substitutions at the same position (A209V and A209E) have been reported in individuals with biochemical findings consistent with OTC deficiency, supporting the functional importance of this region of the protein (Garcia-Perez et al., 1995; Bailly et al., 2015). The A209V variant was apparently de novo in a female with intellectual disability and episodes of coma, while A209E was identified in an adult female with rapidly progressive neuropsychological symptoms and coma (Garcia-Perez et al., 1995; Bailly et al., 2015). However, the A209G variant identified in this individual is observed in 6/47912 (0.013%) alleles from individuals of European background, including one hemizygous individual, in the ExAC dataset (Lek et al., 2016). The A209G variant is a conservative amino acid substitution that occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether the A209G variant is a pathogenic variant or a rare benign variant.