Submissions for variant NM_001271208.2(NEB):c.10347+6C>T (rs141088433)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics,PreventionGenetics	RCV000241822	SCV000307185	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000241822	SCV000528499	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.
Athena Diagnostics Inc	RCV000590292	SCV000614162	benign	not provided	2019-06-27	criteria provided, single submitter	clinical testing
Invitae	RCV001082107	SCV000640486	benign	Nemaline myopathy 2	2019-12-31	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000590292	SCV000697798	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.10347+6C>T variant involves the alteration of a non-conserved intronic nucleotide and 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 925/120680 control chromosomes (19 homozygotes) at a frequency of 0.0076649, 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 5.4% (464/8590 chromosomes). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Therefore, the variant of interest has been classified as Benign.
Illumina Clinical Services Laboratory,Illumina	RCV001082107	SCV001294682	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.