ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1708-1G>C (rs137853280)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004054 SCV000220772 likely pathogenic Wilson disease 2014-10-09 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000004054 SCV000918604 pathogenic Wilson disease 2018-07-23 criteria provided, single submitter clinical testing Variant summary: ATP7B c.1708-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3' acceptor site. At least one publication reports experimental evidence that this variant determines exon 5 skipping (Tsai_1999). The variant allele was found at a frequency of 2.9e-05 in 277094 control chromosomes (gnomAD). The variant, c.1708-1G>C, has been reported in the literature in multiple individuals affected with Wilson Disease (Coffey_2013, Hua_2016, Mukherjee_2014, Tsai_1999). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000004054 SCV001163737 pathogenic Wilson disease criteria provided, single submitter clinical testing
Invitae RCV000004054 SCV001227124 pathogenic Wilson disease 2019-02-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 of the ATP7B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs137853280, ExAC 0.02%). This variant has been observed in several individuals affected with Wilson disease (PMID: 7626145, 27398169, 9829905). This variant is also known in the literature as c.1711-1G>C. ClinVar contains an entry for this variant (Variation ID: 3850). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004054 SCV000024220 pathogenic Wilson disease 2000-11-01 no assertion criteria provided literature only

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