Submissions for variant NM_001164508.2(NEB):c.5370G>A (p.Glu1790=)

gnomAD frequency: 0.30371  dbSNP: rs10170273

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000117761	SCV000269432	benign	not specified	2014-11-26	criteria provided, single submitter	clinical testing	p.Glu1790Glu in exon 44 of NEB: This variant is not expected to have clinical si gnificance because it has been identified in 58% (2157/3720) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/; dbSNP rs10170273).
PreventionGenetics, part of Exact Sciences	RCV000117761	SCV000307361	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000376756	SCV000416991	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	RCV000117761	SCV000519521	benign	not specified	2016-01-05	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587923	SCV000697834	benign	not provided	2017-02-27	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.5370G>A (p.Glu1790Glu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool, Mutation Taster, predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may create an SF2/ASF ESE site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 25704/85158 control chromosomes (4373 homozygotes) at a frequency of 0.3018389, which is approximately 85 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Athena Diagnostics Inc	RCV000587923	SCV001144726	benign	not provided	2019-03-07	criteria provided, single submitter	clinical testing
Invitae	RCV000376756	SCV001716710	benign	Nemaline myopathy 2	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001542883	SCV001761280	benign	Arthrogryposis multiplex congenita 6	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000376756	SCV001761430	benign	Nemaline myopathy 2	2021-07-10	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000117761	SCV000152018	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.	RCV000376756	SCV001453495	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing