Submissions for variant NM_001003800.2(BICD2):c.2321A>G (p.Glu774Gly)

dbSNP: rs398123030

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414546	SCV000491302	pathogenic	not provided	2016-12-06	criteria provided, single submitter	clinical testing	The E774K variant in the BICD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. However, a missense variant at this same codon (E774G) has been reported as a de novo variant in an individual with spinal muscular atrophy (Peeters et al., 2013). The E774K variant is not observed in large population cohorts (Lek et al., 2016). The E774K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret E774K as a pathogenic variant
OMIM	RCV000049277	SCV000077534	pathogenic	Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	2013-06-06	no assertion criteria provided	literature only
Inherited Neuropathy Consortium Ii, University Of Miami	RCV000049277	SCV004011900	uncertain significance	Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	2016-01-06	no assertion criteria provided	literature only