Submissions for variant NM_001164508.2(NEB):c.2310+5G>A

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331741	SCV004039300	likely pathogenic	Nemaline myopathy	2023-08-24	criteria provided, single submitter	clinical testing	Variant summary: NEB c.2310+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a canonical 5' splicing donor site and two predict the variant weakens this site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Moreau-Le Lan_2018), producing a shorter transcript expected to result in an in-frame deletion of 33 amino acids. The variant was absent in 202314 control chromosomes (gnomAD). c.2310+5G>A has been reported in the literature in an individual affected with Nemaline Myopathy who was compound heterozygous with a truncating variant (Moreau-Le Lan_2018). These data suggest the variant may be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 30517146). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.