Submissions for variant NM_020779.4(WDR35):c.2264G>C (p.Arg755Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003056577	SCV003448116	uncertain significance	Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly	2022-10-18	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with WDR35-related conditions. This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 766 of the WDR35 protein (p.Arg766Thr). This variant is present in population databases (rs151208675, gnomAD 0.02%). 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 expected to disrupt WDR35 protein function. 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.
Baylor Genetics	RCV003147817	SCV003836080	uncertain significance	Cranioectodermal dysplasia 2	2022-12-15	criteria provided, single submitter	clinical testing