Submissions for variant NM_001164508.2(NEB):c.914A>G (p.Asp305Gly)

gnomAD frequency: 0.00148  dbSNP: rs36105240

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174105	SCV000225345	benign	not specified	2014-11-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000674805	SCV000417048	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001711465	SCV000730931	benign	not provided	2020-06-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28391287)
Counsyl	RCV000674805	SCV000800204	likely benign	Nemaline myopathy 2	2018-05-24	criteria provided, single submitter	clinical testing
Invitae	RCV000674805	SCV001015699	benign	Nemaline myopathy 2	2024-01-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000674805	SCV001737277	benign	Nemaline myopathy 2	2021-06-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000174105	SCV002103623	benign	not specified	2022-02-24	criteria provided, single submitter	clinical testing	Variant summary: NEB c.914A>G (p.Asp305Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0032 in 248910 control chromosomes, predominantly at a frequency of 0.019 within the East Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 5.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in NEB causing Nemaline Myopathy 2 phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.914A>G in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002505247	SCV002804736	likely benign	Nemaline myopathy 2; Arthrogryposis multiplex congenita 6	2021-11-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000674805	SCV001457268	benign	Nemaline myopathy 2	2020-01-07	no assertion criteria provided	clinical testing