ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.8932_8933insSVAelement

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001089787 SCV001245281 pathogenic not provided 2019-09-21 criteria provided, single submitter clinical testing This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 45 of the USH2A gene (c.8932_8933insSVA), causing a frameshift at codon 2978 (p.Asp2978Glyfs*56). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with USH2A-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) 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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