Submissions for variant NM_001164508.2(NEB):c.16911A>G (p.Pro5637=)

gnomAD frequency: 0.17490  dbSNP: rs33988153

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081112	SCV000113020	benign	not specified	2013-08-23	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000081112	SCV000269411	benign	not specified	2014-11-26	criteria provided, single submitter	clinical testing	p.Pro5637Pro in exon 107 of NEB: This variant is not expected to have clinical s ignificance because it has been identified in 25% (2064/8154) of European Americ an chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/; dbSNP rs33988153).
PreventionGenetics, part of Exact Sciences	RCV000081112	SCV000307257	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000333036	SCV000416924	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	RCV000081112	SCV000519534	benign	not specified	2016-01-25	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	RCV000081112	SCV000919860	benign	not specified	2018-01-02	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.16911A>G (p.Pro5637Pro) variant involves the alteration of a non-conserved nucleotide located in a Nebulin repeat (IPR000900) (InterPro), resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 53815/276434 control chromosomes (6444 homozygotes) at a frequency of 0.1946758, which is approximately 55 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is 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 and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Athena Diagnostics Inc	RCV000992423	SCV001144708	benign	not provided	2019-03-04	criteria provided, single submitter	clinical testing
Invitae	RCV000333036	SCV001730172	benign	Nemaline myopathy 2	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001542983	SCV001761421	benign	Arthrogryposis multiplex congenita 6	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000333036	SCV001761422	benign	Nemaline myopathy 2	2021-07-10	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000081112	SCV000151974	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.	RCV000333036	SCV001455270	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing