ClinVar

Description

This variant was found in heterozygosity in a patient and their father, both with bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). At the time of recruitment, this patient had no other signs associated with a COL11A2-related syndrome. This proband’s father and paternal grandmother both have similar childhood-onset hearing loss. The patient’s father was found to also carry this variant. This variant is a single base pair substitution that is predicted to alter splicing. At the donor splice of COL11A1 exon 52, the sequence change is CGG|gtgagt > CGG|ttgagt, NNSPLICE is 0.99 and 0.00 and MaxEnt is 9.89 and 1.39 for reference and mutant sequences, respectively. The most likely consequence of altered splicing due to this variant is skipping of exon 52 resulting in a 54bp message deletion and an in-frame deletion of 18 amino acids. As of January 2023, this variant has not been reported to ClinVar and is not found on gnomAD. Based on the prediction that this variant leads to a splicing error, co-segregation with the phenotype in the family, and goodness of fit of genotype to phenotype, we conclude that this variant is likely pathogenic.