Submissions for variant NM_001199397.3(NEK1):c.3727G>T (p.Asp1243Tyr)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002510081	SCV002818847	uncertain significance	not provided	2022-09-15	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV003635994	SCV004445631	uncertain significance	Short-rib thoracic dysplasia 6 with or without polydactyly	2023-12-15	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1215 of the NEK1 protein (p.Asp1215Tyr). This variant is present in population databases (rs542986015, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with NEK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1810594). 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 NEK1 protein function with a positive predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences	RCV003926399	SCV004738932	likely benign	NEK1-related disorder	2023-11-16	criteria provided, single submitter	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).