ClinGen Dosage Sensitivity Curation Page

BCLAF1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000006.11) (NC_000006.12)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
28263302 Yuen et al. 2017 reported 2,620 individuals diagnosed with Autism Spectrum Disorders. One patient (AU3865301) was found with a single de novo nonsense mutation in the BLCAF1 gene. However, the clinical details of this patient was not available.
25262651 The collaboration of two consortia (EuroEPINOMICS and Epi4K/EPGP) reported exome-sequencing data of 356 trios with "clasical" epileptic encephalopathies, infantile spasms and Lennox Gastaut sydrome. One patient (isnd29975cb1) with infantile spasms was found with a single de novo nonsense mutation in the BCLAF1 gene. However, the clinical details of this patient was not available.

Haploinsufficiency phenotype comments:

There were numerous entries from more than three independent studies in the Database of Genomic Variants (DGVs) showing exonic deletion within the BCLAF1 gene. Therefore, intragenic heterozygous deletion of BCLAF1 gene is unlikely to be associated with neurodevelopmental disorders. Notably, the ClinVar Variants database had five benign missense mutations (Variation ID: 402423, 402422, 402421, 402420 and 402419) and one uncertain splice donor mutation (Variation ID: 402424) (Last reviewed 29/03/2016). There were no functional studies to demonstrate BCLAF1 was implicated in neurodevelopmental disorders such as autism or epilepsy. However, McPherson et al. (2009) (PMID: 19008920) showed that heterozygous bclaf1 mice had an intermediate reduction in T lymphocytes proliferation and activation responses, suggesting BCLAF1 had a critical role in lung development and proper functioning of the immune system. Also, Lowe et al. (2018) (PMID: 29466738) demonstrated in knockdown Bclaf1 mice that BCLAF1 cooperatively interacted with Cry2 (i.e. in CCND1 and TMEM176B gene regulation) to promote myoblast proliferation and subsequently myocyte fusion to form myotubes.

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