Submissions for variant NM_001199397.3(NEK1):c.924T>G (p.Ile308Met)

gnomAD frequency: 0.00151  dbSNP: rs10034957

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001560050	SCV000884230	uncertain significance	not provided	2023-11-22	criteria provided, single submitter	clinical testing	The NEK1 c.924T>G; p.Ile308Met variant (rs10034957), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.05% (identified on 136 out of 277,020 chromosomes). The isoleucine at position 308 is highly conserved, considering 10 species, and computational analyses of the effects of the p.Ile308Met variant on protein structure and function make conflicting predictions (SIFT: tolerated, PolyPhen-2: probably damaging). Based on the available information, the clinical significance of the p.Ile308Met variant cannot be determined with certainty.
Invitae	RCV001088521	SCV001092355	likely benign	Short-rib thoracic dysplasia 6 with or without polydactyly	2024-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001088521	SCV001306884	likely benign	Short-rib thoracic dysplasia 6 with or without polydactyly	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001560050	SCV001782384	likely benign	not provided	2021-02-09	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001088521	SCV003813597	uncertain significance	Short-rib thoracic dysplasia 6 with or without polydactyly	2022-08-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003938133	SCV004747776	likely benign	NEK1-related disorder	2020-04-29	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).