Submissions for variant NM_000053.4(ATP7B):c.*16G>A

gnomAD frequency: 0.00105  dbSNP: rs193922100

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001420713	SCV000052031	uncertain significance	not specified	2024-04-26	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.*16G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0011 in 1612330 control chromosomes, predominantly at a frequency of 0.0013 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ATP7B causing Wilson Disease (0.0011 vs 0.0054), allowing no strong conclusion about variant significance. c.*16G>A has been reported in the literature as a VUS in at least one individual affected with Wilson Disease as well as in unaffected controls (example, Stalke_2018, Coffey_2013). These reports do not provide unequivocal conclusions about association of the variant with Wilson Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23518715, 28776642). ClinVar contains an entry for this variant (Variation ID: 35734). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Illumina Laboratory Services, Illumina	RCV000029383	SCV000384643	uncertain significance	Wilson disease	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000029383	SCV001006029	benign	Wilson disease	2023-09-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000865113	SCV001811453	likely benign	not provided	2018-01-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28776642)