Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000693441 | SCV000821311 | uncertain significance | Short-rib thoracic dysplasia 8 with or without polydactyly | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp23*) in the WDR60 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is present in population databases (rs202111347, gnomAD 0.7%). This variant has not been reported in the literature in individuals affected with WDR60-related conditions. ClinVar contains an entry for this variant (Variation ID: 572127). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Laboratory for Molecular Medicine, |
RCV000826084 | SCV000967579 | uncertain significance | not specified | 2018-10-12 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Trp23X varian t in WDR60 has not been reported in individuals with short rib-thoracic dysplasi a, but has been identified in 0.7% (69/9846) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD). This nonsense variant leads to a prema ture termination codon at position 23, however, it only occurs in one transcript of the gene (NM_018051.4). This variant also occurs in the last bases of the ex on, which is part of the 5? splice region and computational tools predict altere d splicing. In summary, the clinical significance of the p.Trp23X variant is unc ertain. ACMG/AMP Criteria applied: BS1_Supporting. |
| Reproductive Health Research and Development, |
RCV000693441 | SCV001142378 | uncertain significance | Short-rib thoracic dysplasia 8 with or without polydactyly | 2020-01-06 | no assertion criteria provided | curation | NM_018051.4:c.69G>A in the WDR60 gene has an allele frequency of 0.007 in Ashkenazi Jewish subpopulation in the gnomAD database. This sequence change creates a premature translational stop signal (p.Trp23*) in the WDR60 gene. Pathogenic computational verdict because pathogenic predictions from DANN, EIGEN, FATHMM-MKL and MutationTaster . It is expected to result in an absent or disrupted protein product. Taken together, we interprete this variant as variant of uncertain significance (VUS). ACMG/AMP Criteria applied: PVS1; PP3. |