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

Total submissions: 2

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
Integrated Genetics/Laboratory Corporation of America	RCV000169063	SCV000694425	likely pathogenic	Wilson disease	2017-08-21	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.2575+1G>C variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict a significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 1/120766 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). This variant was reported in multiple Wilson Disease patients, including in two of British origin in compound heterozygosity with ATP7B c.331C>T/p.Gln111Term (not in our internal database, DM in HGMD). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic. Taken together, this variant is classified as likely pathogenic.