Variants in BRSK2 were first reported in relation to complex neurodevelopmental disorder as early as 2012 (O’Roak et al., PMID: 22495309), and later reported in at least another 18 probands in 6 publications (PMIDs: 25363760, 28135719, 30879638, 31452935, 31981491, 33057194). Affected individuals have speech delay, intellectual disability, motor delay, behavioral issues including autism, and facial dysmorphism. Variant types include frameshift, nonsense, splice site, in-frame deletions, and missense variants, with most variants occurring de novo. Because functional studies were not performed, missense and in-frame deletions were only scored 0.1 points. The mechanism for disease is haploinsufficiency. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. This gene-disease association is also supported by phenotype characterization in a knockout mouse model (1.5 points). In summary, BRSK2 is definitely associated with autosomal dominant complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 02/03/2021 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.