Description
The p.Val415del variant in WFS1 has been reported in >10 individuals with Wolfra m syndrome (Hardy 1999, Smith 2004, Hansen 2005, Gasparin 2009, Chaussenot 2011, Rohayem 2011, Rendtorff 2011, de Heredia ML 2013, Bodoor 2016) and segregated i n 7 affected relatives (Hardy 1999, Hansen 2005, Gasparin 2009, Rendtorff 2011, Bodoor 2016). All of these individuals were homozygous or compound heterozygous. This variant has also been reported in ClinVar (Variation ID: 215406). This var iant was identified in 9/33582 Latino chromosomes by the Genome Aggregation Data base (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs750767821); however, its frequency is low enough to be consistent with a recessive carrier frequency. In addition, in vitro studies suggest that the p.Val415del variant may impact expr ession of WFS1 (Rendtorff 2011). In summary, this variant meets criteria to be c lassified as pathogenic for autosomal recessive Wolfram syndrome based upon repo rted familial cases, low frequency in controls, and functional evidence.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | not provided | not provided | not provided | not provided | | 1 | not provided | 1 | not provided |
