Submissions for variant NM_001271208.2(NEB):c.6184-14T>A (rs10173335)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000217223	SCV000269434	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	6184-14T>A in intron 48 of NEB: This variant is not expected to have clinical si gnificance because it has been identified in 22.5% (811/3602) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs10173335).
PreventionGenetics,PreventionGenetics	RCV000217223	SCV000307379	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000306126	SCV000416978	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	RCV000217223	SCV000519852	benign	not specified	2016-02-15	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.
Integrated Genetics/Laboratory Corporation of America	RCV000589625	SCV000697835	benign	not provided	2017-02-27	criteria provided, single submitter	clinical testing	Variant summary: c.6184-14T>A in NEB gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect the normal splicing pattern, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.06562 (7599 / 115796 chrs tested), including numerous homozygotes across multiple ethnicities. The observed frequency exceed the maximum expected allele frequency for a pathogenic variant of 0.0035. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but cited as Benign by reputable databases/clinical laboratories. Considering all, the variant was classified as Benign.