Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000826122 | SCV000967631 | likely pathogenic | Rare genetic deafness | 2017-10-06 | criteria provided, single submitter | clinical testing | The c.4574-2A>G (NM_173591.3) variant in OTOGL has not been previously reported in individuals with hearing loss, but has been identified in 1/16,128 East Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.or g; dbSNP rs368266167). Although this variant has been seen in the general popula tion, its frequency is low enough to be consistent with a recessive carrier freq uency. This variant occurs in the invariant region (+/- 1,2) of the splice cons ensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Biallelic loss of function of the OTOGL gene has been associ ated with hearing loss. In summary, although additional studies are required to fully establish a null impact, the c.4574-2A>G variant is likely pathogenic for hearing loss in an autosomal recessive manner based on its predicted impact on t he protein. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015). |