De novo variants in the KATNAL2 gene have been identified in autistic probands from simplex families in two separate reports (PMIDs 22495306 and 22495309). Two of these variants are stop-gains and many are missense variants in EVS. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified KATNAL2 as a gene meeting high statistical significance with a FDR â?¤0.01, meaning that this gene had a â?¥99% chance of being a true autism gene (PMID 25363760). A third de novo loss-of-function variant and a likely damaging de novo missense variant in KATNAL2 were identified in probands from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.
Category 1 - High Confidence
Recurrent and convincing mutations accompanied by a rigorous statistical comparison with the mutation frequency in controls, and independent replication. Full sequencing of a comparable number of cases and controls is required. Convincing is defined as ?likely to be functional?, or showing perfect segregation of mutations and phenotype in a large pedigree.