Description
A variant of uncertain significance has been identified in the CHRNA2 gene. The T47M variant has been reported previously in two unrelated individuals with idiopathic generalized epilepsy; however, no additional information was provided (Klassen et al., 2011; Wei et al., 2017). The T47M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the T47M variant is observed in 111/126604 (0.1%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). Additionally, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
