ClinGen Dosage Sensitivity Curation Page

CRYBA1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Three types of mutations in CRYBA1 have been reported in association with congenital cataracts of various types: IVS3+1 splice mutation (multiple families), IVS3+2 (one family), and a 3-base pair deletion (G91del) (multiple families) (PMIDs: 7573044, 9788845, 14598164, 15016766, 22919269, 22665976). The G91 del mutation has been shown to lead to misfolded proteins with altered hydrophobicity (PMID: 20300566, 15016766) and the splice mutations result in aberrant splicing. While the splice variants would typically be considered likely loss of function mutations, authors speculate that all of these mutations likely lead to protein aggregation as the mechanism for cataract formation. It is not clear that a whole gene deletion or mutation that results in loss of protein would have this same effect.

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