Submissions for variant NM_001164508.2(NEB):c.8318G>A (p.Arg2773Gln)

gnomAD frequency: 0.01764  dbSNP: rs35974308

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000117773	SCV000269438	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Arg2773Gln in exon 60 of NEB: This variant is not expected to have clinical si gnificance because it has been identified in 2.8% (234/8218) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs35974308).
PreventionGenetics, part of Exact Sciences	RCV000117773	SCV000307395	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000556961	SCV000416958	benign	Nemaline myopathy 2	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000117773	SCV000519525	benign	not specified	2016-03-12	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.
Athena Diagnostics	RCV000117773	SCV000614184	benign	not specified	2020-10-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000556961	SCV000640872	benign	Nemaline myopathy 2	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590623	SCV000697841	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.8318G>A (p.Arg2773Gln) variant involves the alteration of a conserved nucleotide and 3/4 in silico tools (SNPs&GO not captured here due to low reliability index) predict a damaging outcome. This variant was found in 2834/120142 control chromosomes (37 homozygotes) from ExAC at a frequency of 0.0235888, which is approximately 7 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), strongly supporting that this variant is likely a benign polymorphism. The variant is more common in East Asian sub-population with allele frequency of 4.5% (751/16334 chromosomes). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000590623	SCV005238904	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000117773	SCV000152033	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Natera, Inc.	RCV000556961	SCV001463530	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000117773	SCV002034154	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000117773	SCV002035780	benign	not specified		no assertion criteria provided	clinical testing