Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001449690 | SCV001652942 | likely pathogenic | Rare genetic deafness | 2020-06-25 | criteria provided, single submitter | clinical testing | The c.4055-1G>C variant in OTOGL has not been previously reported in individuals with hearing loss but has been identified in 0.022% (4/17858) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). However, this frequency is low enough to be consistent with a recessive allele frequency. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the OTOGL gene is an established disease mechanism in autosomal recessive hearing loss. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM2. |