Submissions for variant NM_000053.4(ATP7B):c.2785A>G (p.Ile929Val)

gnomAD frequency: 0.00038  dbSNP: rs534960245

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174213	SCV000225476	benign	not specified	2015-02-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587605	SCV000694430	benign	not provided	2016-10-06	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.2785A>G (p.Ile929Val) variant involves the alteration of a non-conserved nucleotide. Ile929 is located in the transmembrane domain, is highly conserved across species, and 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). However, yeast functional analyses showed no significant effect of this I929V. Additionally, this variant was found in 131/121316 control chromosomes (1 homozygote), predominantly observed in the East Asian subpopulation at a frequency of 0.0131243 (113/8610). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple sources, including a clinical diagnostic laboratory, a database, and publications, classified this variant as benign. Taken together, this variant is classified as Benign.
GeneDx	RCV000174213	SCV000730409	likely benign	not specified	2017-10-03	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081569	SCV000752280	benign	Wilson disease	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001081569	SCV001270798	uncertain significance	Wilson disease	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001081569	SCV001977151	likely benign	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001081569	SCV004362481	likely benign	Wilson disease	2022-09-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001081569	SCV001456173	benign	Wilson disease	2020-04-15	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955024	SCV004768097	benign	ATP7B-related disorder	2019-08-09	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).