Submissions for variant NM_000053.4(ATP7B):c.2575+1G>C (rs766149114)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169063	SCV000220227	likely pathogenic	Wilson disease	2014-04-09	criteria provided, single submitter	literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169063	SCV000694425	likely pathogenic	Wilson disease	2021-02-28	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.2575+1G>C 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: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 249552 control chromosomes. c.2575+1G>C has been reported in the literature in individuals affected with Wilson Disease and subsequently cited by others (example, Thomas_1995, Coffey_2013, Singh_2019). 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.
GeneDx	RCV001582664	SCV001813009	pathogenic	not provided	2020-06-04	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 7626145, 23518715)