Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000555798 | SCV000660423 | uncertain significance | Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly | 2020-02-11 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a WDR35-related disease. This sequence change replaces proline with alanine at codon 222 of the WDR35 protein (p.Pro222Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. |