ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3557-6C>T (rs140708492)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000248416 SCV000301719 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029371 SCV000384651 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.
GeneDx RCV000488125 SCV000527871 likely benign not provided 2021-03-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488125 SCV000574958 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000029371 SCV000602595 benign Wilson disease 2018-07-25 criteria provided, single submitter clinical testing
Invitae RCV000029371 SCV000626856 benign Wilson disease 2020-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000248416 SCV000694451 uncertain significance not specified 2016-06-28 criteria provided, single submitter clinical testing Variant summary: The c.c.3557-6C>T variant involves the alteration of a non-conserved nucleotide resulting in an intronic change. This variant is located at a position that is not widely known to affect splicing, 4/5 splicing prediction tools predict no significant effect on splicing, and Mutation Taster predicts the variant to be a polymorphism. This variant was found in 324/122184 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0037672 (250/66362). This subpopulation frequency is lower than the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), but is high enough to suggest that variant could possibly be a benign polymorphism. Additionally, the variant is regarded as a benign variant in literature (Thomas _1995; Mukherjee_2014) and in at least one database (University of Alberta WD database); however no definite evidence was provided to independently evaluate. There was an internal finding that two variants (c.1922T>C (VUS) and c.2731-2A>G (disease variant)) were identified to co-occur with the variant of interest in a subject undergoing ATP7B gene testing. These variants may explain WD phenotype, albeit phase of the variants would need to be assessed and c.1922T>C has not yet been classified as a disease variant. Taken together, this variant has been classified as a VUS-possibly benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000029371 SCV000733355 likely benign Wilson disease no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000488125 SCV001808826 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000488125 SCV001931634 likely benign not provided no assertion criteria provided clinical testing

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