Submissions for variant NM_014141.6(CNTNAP2):c.2705C>T (p.Pro902Leu)

gnomAD frequency: 0.00050  dbSNP: rs202095023

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187218	SCV000240800	uncertain significance	not provided	2018-03-06	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CNTNAP2 gene. The P902L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P902L variant is observed in 113/25782 (0.4%) alleles from individuals of Finnish background, including 1 homozygous individual, in large population cohorts (Lek et al., 2016). The P902L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV001079100	SCV001002822	likely benign	Cortical dysplasia-focal epilepsy syndrome	2024-01-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002433836	SCV002744897	uncertain significance	Inborn genetic diseases	2017-10-30	criteria provided, single submitter	clinical testing	The p.P902L variant (also known as c.2705C>T), located in coding exon 17 of the CNTNAP2 gene, results from a C to T substitution at nucleotide position 2705. The proline at codon 902 is replaced by leucine, an amino acid with similar properties. This amino acid position is not conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.