Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482448 | SCV000574098 | uncertain significance | not provided | 2017-03-16 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CNTNAP2 gene. The c.252 G>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.252 G>C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.252 G>C enhances or creates a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If the c.252 G>C does not affect splicing, it will result in a W84C missense substitution. The W84C 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. This substitution occurs at a position that is conserved across species, and 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 this variant is a pathogenic variant or a rare benign variant. |