Submissions for variant NM_001408.3(CELSR2):c.5974G>A (p.Gly1992Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002957565	SCV003270068	uncertain significance	not provided	2022-08-06	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with CELSR2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 disruptive. This variant is present in population databases (rs12567377, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1992 of the CELSR2 protein (p.Gly1992Arg).
PreventionGenetics, part of Exact Sciences	RCV003926564	SCV004738934	likely benign	CELSR2-related disorder	2022-03-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).