Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018350 | SCV004848079 | likely pathogenic | Amelogenesis imperfecta | 2017-08-02 | criteria provided, single submitter | clinical testing | The p.Trp674MetfsX3 variant in WDR72 has not been previously reported in individuals with disease, but has been identified in 5/23,944 of African chromosomes by the Genome Aggregation Consortium gnomAD http://gnomad.broadinstitute.org; dbSNP rs779460257). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 674 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the WDR72 gene is associated to non-syndromic amelogenesis imperfecta. In summary, although additional studies are required to fully establish its clinical significance, the p.Trp674MetfsX3 variant in WDR72 is likely pathogenic. |