ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.5858-1G>A (rs397518023)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041871 SCV000065567 pathogenic Rare genetic deafness 2012-01-18 criteria provided, single submitter clinical testing The 5858-1G>A variant in USH2A has not been reported in the literature nor previ ously identified by our laboratory. However, the 5858-1G>A variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the inv ariant region of the splice consensus sequence. In summary, this variant meets o ur criteria to be classified as pathogenic.
Counsyl RCV000665613 SCV000789763 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-02-16 criteria provided, single submitter clinical testing
Invitae RCV000821430 SCV000962185 pathogenic not provided 2020-03-29 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 29 of the USH2A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal recessive USH2A-related conditions (PMID: 25649381, 30948794, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 48545). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). For these reasons, this variant has been classified as Pathogenic.

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