Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000604368 | SCV000731982 | likely pathogenic | Amelogenesis imperfecta | 2018-01-24 | criteria provided, single submitter | clinical testing | The p.Arg30X variant (NM_182758.2 c.88C>T) in WDR72 has not been previously repo rted in the literature, but has been identified in 2/34392 of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; d bSNP rs770804941). Although this variant has been seen in the general population , its frequency is low enough to be consistent with a recessive carrier frequenc y. This nonsense variant leads to a premature termination codon at position 30, which is predicted to lead to a truncated or absent protein. Biallelic loss of f unction of the WDR72 gene has been associated with amelogenesis imperfecta. In s ummary, although additional studies are required to fully establish its clinical significance, the p.Arg30X variant is likely pathogenic based on a predicted nu ll effect. ACMG/AMP Criteria applied: PVS1; PM2 (Richards 2015). |
| Genetics and Molecular Pathology, |
RCV002272302 | SCV002556924 | likely pathogenic | Amelogenesis imperfecta hypomaturation type 2A3 | 2021-07-30 | criteria provided, single submitter | clinical testing | The WDR72 c.88C>T variant is classified as a LIKELY PATHOGENIC variant (PVS1, PM2) The variant is a single nucleotide change from a cytosine to a thymine at position 88 which is predicted to change the Arginine at position 30 in the protein to a premature STOP codon, which is predicted to lead to a truncated or absent protein (PVS1). The variant is in dbSNP (rs770804941) but its low frequency in population databases (gnomAD 7/282418, 0 homozygotes) is consistent with a recessive carrier frequency (PM2). The variant has been reported in the ClinVar as likely pathogenic (Variation ID: 517616), and in the HGMD as VUS (Accession#: CM190501). |
| Fulgent Genetics, |
RCV002272302 | SCV002810867 | likely pathogenic | Amelogenesis imperfecta hypomaturation type 2A3 | 2021-07-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV005250083 | SCV005900908 | pathogenic | not provided | 2024-09-17 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31589614, 33033857, 36836560, 30609409) |