ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency 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.

Haploinsufficiency phenotype comments:

This gene is extremely constrained against haploinsufficency in the human genome. Currently at least three independent null variants had been reported in patients with developmental delay (DD), autism spectrum disorder (ASD) and/or intellectual disability (ID). Multiple patients with large deletion involving this gene (and many other genes) exhibited DD/ID/ASD. No deletion involving NCKAP1 was reported in normal populations.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No evidence suggesting triplosensitivity of NCKAP1 gene.