Submissions for variant NM_000053.4(ATP7B):c.628A>G (p.Ile210Val)

gnomAD frequency: 0.00204  dbSNP: rs61733680

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000436240	SCV000109893	uncertain significance	not provided	2013-02-26	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000436240	SCV000510651	likely benign	not provided	2016-10-11	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001001253	SCV000626867	likely benign	Wilson disease	2025-01-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000436240	SCV000694469	uncertain significance	not provided	2016-06-15	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.628A>G (p.Ile210Val) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index. This variant was found in 75/120704 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0066394 (65/9790). This frequency is slightly greater than the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is variant may be a benign polymorphism found primarily in the populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. In addition, one clinical diagnostic laboratory classified this variant as a VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001253	SCV001158422	uncertain significance	Wilson disease	2022-03-08	criteria provided, single submitter	clinical testing	The ATP7B c.628A>G; p.Ile210Val variant (rs61733680), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 92390). This variant is found in the African population with an overall allele frequency of 0.63% (153/24192 alleles) in the Genome Aggregation Database. The isoleucine at codon 210 is moderately conserved and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.201). However, due to limited information, the clinical significance of the p.Ile210Val variant is uncertain at this time.
GeneDx	RCV000436240	SCV001812199	likely benign	not provided	2021-06-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001001253	SCV001977190	likely benign	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001001253	SCV004821491	uncertain significance	Wilson disease	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with valine at codon 210 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with Wilson disease in the literature. This variant has been identified in 176/280802 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV003935015	SCV004762622	likely benign	ATP7B-related disorder	2020-09-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).