Submissions for variant NM_001164508.2(NEB):c.21585A>G (p.Thr7195=)

gnomAD frequency: 0.55659  dbSNP: rs4664475

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081120	SCV000113028	benign	not specified	2013-04-05	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000081120	SCV000269418	benign	not specified	2014-11-26	criteria provided, single submitter	clinical testing	This is a RefSeq error. The reference base (c.21690A) is the minor allele. This allele (A) has been identified in 38% (3158/8354) of European American chromosom es and 59% (2374/4046) of African American chromosomes by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs4664475) and thus meets criteria to be classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000081120	SCV000307300	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000375369	SCV000416848	benign	Nemaline myopathy 2	2018-01-12	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590486	SCV000697801	benign	not provided	2017-02-27	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.21690A>G (p.Thr7230Thr) variant involves the alteration of a non-conserved nucleotide, 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. This variant was found in 69172/118646 control chromosomes (20606 homozygotes) at a frequency of 0.5830116, which is approximately 165 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), evidence that this variant is a benign polymorphism. Multiple clinical diagnostic laboratories cite the variant as "benign." Taken together, this variant is classified as benign.
GeneDx	RCV000081120	SCV000725021	benign	not specified	2017-11-03	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	RCV000590486	SCV001144715	benign	not provided	2019-02-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000375369	SCV001729455	benign	Nemaline myopathy 2	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001543074	SCV001761572	benign	Arthrogryposis multiplex congenita 6	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000375369	SCV001761573	benign	Nemaline myopathy 2	2021-07-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590486	SCV005245925	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000081120	SCV000151993	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.	RCV000375369	SCV001463291	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing