Submissions for variant NM_000053.4(ATP7B):c.3556+1G>A (rs184388696)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169452	SCV000220873	likely pathogenic	Wilson disease	2014-11-11	criteria provided, single submitter	literature only
Integrated Genetics/Laboratory Corporation of America	RCV000169452	SCV000694449	likely pathogenic	Wilson disease	2019-04-01	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.3556+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.1e-06 in 246256 control chromosomes (gnomAD). c.3556+1G>A has been reported in the literature in two unrelated individuals affected with Wilson Disease (Thomas 1995, Ljubic 2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.