ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12295-2A>G (rs151148854)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041714 SCV000065410 pathogenic Rare genetic deafness 2012-08-28 criteria provided, single submitter clinical testing
Counsyl RCV000670554 SCV000795417 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-11-14 criteria provided, single submitter clinical testing
Invitae RCV001057968 SCV001222499 pathogenic not provided 2020-08-20 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 62 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). Disruption of this splice site has been observed in individual(s) with clinical features of Usher syndrome (PMID: 30459346, Invitae). ClinVar contains an entry for this variant (Variation ID: 48392). 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.
Blueprint Genetics RCV001074339 SCV001239914 likely pathogenic Retinal dystrophy 2019-07-12 criteria provided, single submitter clinical testing
GeneDx RCV001057968 SCV001777205 pathogenic not provided 2021-05-05 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar as pathogenic or likely pathogenic but additional evidence is not available (SCV000065410.5, SCV000795417.1; Landrum et al., 2016); Has not been previously published as pathogenic or benign to our knowledge

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