Submissions for variant NM_001199397.3(NEK1):c.2137G>A (p.Val713Met)

gnomAD frequency: 0.00063  dbSNP: rs199827465

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Genomic and Experimental Medicine, University of Edinburgh	RCV000492577	SCV000323214	likely benign	Motor neuron disease	2016-08-31	criteria provided, single submitter	case-control
Eurofins Ntd Llc (ga)	RCV000334816	SCV000332208	likely benign	not specified	2018-05-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000334816	SCV000525783	benign	not specified	2016-05-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756420	SCV000884229	likely benign	not provided	2017-12-23	criteria provided, single submitter	clinical testing	The c.2053G>A p.Val685Met variant (rs199827465), to our knowledge, is not reported in the medical literature nor has it been previously identified by our laboratory, but is listed as benign/likely benign/VUS in ClinVar (ClinVar ID:266049). This variant is listed in the genome Aggregation Database (gnomAD) with an Ashkenazi Jewish population frequency of 1.2% (identified on 120 out of 10,056 chromosomes). The valine at position 685 is weakly conserved considering 10 species and computational analyses of the effects of the p.Val685Met variant on protein structure and function predict no harmful effects (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the p.Val685Met variant is likely to be benign.
Illumina Laboratory Services, Illumina	RCV001148831	SCV001309743	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001148831	SCV002410549	benign	Short-rib thoracic dysplasia 6 with or without polydactyly	2024-01-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756420	SCV004151814	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	NEK1: BP4, BS1