ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.486-14G>A (rs374536346)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414183 SCV000490866 pathogenic not provided 2015-07-01 criteria provided, single submitter clinical testing The c.486-14 G>A splice site variant in the USH2A gene has been previously reported in association with Usher syndrome type 2A (Le Guedard-Mereuze et al., 2010; Baux et al., 2014). This variant reduces the quality of the splice acceptor site in intron 2, and is expected to cause abnormal gene splicing. Specifically, it is predicted that a de novo splice acceptor site is created that competes with the authentic 3' splice site and that the use of this upstream de novo 3' splice site causes an insertion of intronic sequences into the mature transcripts (Le Guedard-Mereuze et al., 2010). Therefore, we interpret this variant as pathogenic.
Counsyl RCV000673542 SCV000798754 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2018-03-23 criteria provided, single submitter clinical testing
Invitae RCV000414183 SCV001236140 pathogenic not provided 2020-10-04 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein. This variant is present in population databases (rs374536346, ExAC 0.009%). This variant has been observed in individual(s) with retinitis pigmentosa and Usher syndrome (PMID: 27957503, 22334370, 28944237). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372543). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20052763). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075754 SCV001241384 pathogenic Retinal dystrophy 2019-06-07 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000678652 SCV001934220 pathogenic Retinitis pigmentosa 39 2020-10-06 criteria provided, single submitter clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000678652 SCV000804743 pathogenic Retinitis pigmentosa 39 2016-09-01 no assertion criteria provided clinical testing

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