Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000218080 | SCV000271378 | pathogenic | Rare genetic deafness | 2015-09-17 | criteria provided, single submitter | clinical testing | The c.1063-1G>T variant in GPSM2 has not been previously reported in individuals with hearing loss or Chudley-McCullough syndrome, but has been identified in 1/ 65476 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs773068151). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a rec essive carrier frequency. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing lead ing to an abnormal or absent protein. Loss-of-function variants in the GPSM2 gen e are associated with Chudley-McCullough syndrome, an autosomal recessive condit ion with congenital hearing loss and brain abnormalities with typically normal c ognition. In summary, this variant meets our criteria to be classified as pathog enic for hearing loss in an autosomal recessive manner based on the predicted im pact of the variant. |
| Gene |
RCV004721303 | SCV005327935 | likely pathogenic | not provided | 2024-03-19 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |