Submissions for variant NM_001164508.2(NEB):c.18693G>C (p.Ala6231=)

gnomAD frequency: 0.00448  dbSNP: rs141338915

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000117729	SCV000233226	benign	not specified	2015-02-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000117729	SCV000307269	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001082595	SCV000416899	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	RCV000117729	SCV000528776	benign	not specified	2016-07-08	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.
Invitae	RCV001082595	SCV000640628	benign	Nemaline myopathy 2	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587974	SCV000697808	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.18693G>C (p.Ala6231Ala) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change that is located at the last nucleotide of exon 119, therefore suggesting the variant could affect splicing. One in silico tool (mutation taster) predicts a damaging outcome for this variant. 3/5 splice prediction tools predict an impact on normal splicing and ESE finder predicts that this variant may affect ESE site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 703/120702 control chromosomes (16 homozygotes) from ExAC at a frequency of 0.0058243, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is likely a benign polymorphism. The variant is more common in East Asian sub-population with allele frequency of 4.7% (408/8614 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.
Athena Diagnostics Inc	RCV000587974	SCV001144709	benign	not provided	2019-06-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002505045	SCV002810055	likely benign	Nemaline myopathy 2; Arthrogryposis multiplex congenita 6	2022-04-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000117729	SCV000151980	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.	RCV001082595	SCV001453278	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000587974	SCV001800226	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000587974	SCV001927750	likely benign	not provided		no assertion criteria provided	clinical testing