ClinGen Dosage Sensitivity Curation Page

CDC42BPB

  • Curation Status: Complete

Location Information

  • 14q32.32
  • GRCh37/hg19 chr14: 103,398,716-103,523,742
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr14: 102,932,379-103,057,405
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000014.8) (NC_000014.9)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22495309 O?Roak et al. (2012) describe a male (sample 13606.p1) with sporadic autism spectrum disorder (ASD) who has a nonverbal IQ (NVIQ) of 60 (Table 1). Whole exome sequencing of the affected individual identified a de novo heterozygous nonsense variant in exon 16 of the CDC42BPB gene (Chr14:103434646G>A) (Supplementary Table 3). This variant causes a premature termination at codon 764 of the CDC42BPB protein (p.Arg764*). This variant was not observed in either parent nor in the unaffected female sibling (13606.s1, Supplementary Table 5). Of note, the affected individual also had a de novo heterozygous missense variant in the H2AFV gene (Chr7:44875121G>A, p.Arg81Cys) which was not observed in either parent nor in the unaffected female sibling. However, the nonsense variant in CDC42BPB was identified, per the authors to be a top ASD risk contributing variant based on the deleteriousness of the variant, functional evidence, or previous studies whereas the missense variant in H2AFV was not. In addition, CDC42BPB was mapped to a highly interconnected beta-catenin/chromatin remodeling protein network ranked significantly for autism candidate genes. This variant is absent from gnomAD as of October 2018.
28263302 Yuen et al. (2017) identified a de novo frameshift deletion in the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder (sample AU079605; Supplementary Table 4). Within this study cohort no other variants in CDC42BPB were observed in any of the other 2,260 autism cases or in any of the 2,573 controls.

Haploinsufficiency phenotype comments:

De Rubeis et al. (2014; PMID: 25363760) identified a de novo missense variant in exon 36 of the CDC42BPB gene (Chr14:103404494C>T) in an individual with autism spectrum disorder (ASD) (Supplementary Table 3). This variant causes an amino acid change from a valine to a methionine at codon 1651 (p.Val1651Met). In gnomAD this variant has an allele frequency of 0.00001446 (4/276640 alleles, rs201627729). Polyphen and SIFT identify this variant as benign and tolerated, respectively. Within this study cohort no other variants in CDC42BPB were observed in any of the other 3,870 autism cases or in any of the 9,937 ancestry-matched or parental controls.

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