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. |