Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000421226 | SCV000521361 | pathogenic | not provided | 2016-12-15 | criteria provided, single submitter | clinical testing | The W978X variant in the WDR72 gene has been reported previously in the homozygous state in an individual with hypomaturation amelogenesis imperfecta (El-Sayed et al., 2009). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W978X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret W978X as a pathogenic variant. |
3billion | RCV000000256 | SCV002058755 | pathogenic | Amelogenesis imperfecta hypomaturation type 2A3 | 2022-01-03 | criteria provided, single submitter | clinical testing | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported to be associated with WDR72 related disorder (ClinVar ID: VCV000000232, PMID:19853237). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). Each parent is heterozygous for the variant (PM3_P, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
OMIM | RCV000000256 | SCV000020400 | pathogenic | Amelogenesis imperfecta hypomaturation type 2A3 | 2009-11-01 | no assertion criteria provided | literature only | |
Department Of Genetics, |
RCV000000256 | SCV000891566 | pathogenic | Amelogenesis imperfecta hypomaturation type 2A3 | 2017-12-30 | no assertion criteria provided | curation |