Submissions for variant NM_000052.7(ATP7A):c.2406G>C (p.Lys802Asn)

dbSNP: rs2077838704

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812938	SCV001472540	likely pathogenic	not provided	2019-12-10	criteria provided, single submitter	clinical testing	The ATP7A c.2406G>C; p.Lys802Asn variant is reported in the literature in at least one individual affected with Menkes disease (Skjorringe 2012, Skjorringe 2017). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant occurs in the last nucleotide of exon 10, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. Consistent with these predictions, analysis of patient mRNA shows skipping of exon 10 in nearly all transcripts, which correlates with the loss of protein expression in patient fibroblasts (Skjorringe 2017). Based on available information, this variant is considered to be likely pathogenic. References: Skjorringe T et al. Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease. Sci Rep. 2017 Apr 7;7(1):757. Skjorringe T et al. Splice site mutations in the ATP7A gene. PLoS One. 2011 Apr 11;6(4):e18599.
Inherited Neuropathy Consortium Ii, University Of Miami	RCV003311976	SCV004012047	uncertain significance	Menkes kinky-hair syndrome	2016-01-06	no assertion criteria provided	literature only