ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
27632392 Freed and Pevsner (2016) reported a de novo (potentially mosaic) frameshift variant (NM_205842.2:c.524_525insGT/p.Ala176X) in a patient with autism spectrum disorder.
27824329 Wang et al., (2016) detected a de novo splicing variant c.3180+ 1G>A in a Chinese patient with ASD and global developmental delay among 1,543 probands with ASD.
28940097 Anazi et al. (2017) reported a heterozygous nonsense variant c.3298G>T:p.Glu1100* segregated with intellectual disability in a large multigenerational family in an effort for discovering novel genetic causes of intellectual disability. This four generation pedigree had a total of 13 affected (not all were genotyped). Seven heterzygous carriers that were genotyped were all affected. Two unaffected individuals had normal genotype. The gene expression pattern suppport the involvement of NCKAP1 in brain function.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.