Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002976188 | SCV003289052 | uncertain significance | Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 | 2023-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 805 of the WDR19 protein (p.Asp805Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of WDR19-related conditions (Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WDR19 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |