ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9258+1G>T

dbSNP: rs748810737
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671455 SCV000796431 likely pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2017-12-14 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075805 SCV001241440 likely pathogenic Retinal dystrophy 2019-07-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855560 SCV002200265 pathogenic not provided 2022-10-18 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individuals with retinitis pigmentosa (PMID: 30902645, 31047384). ClinVar contains an entry for this variant (Variation ID: 555604). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 46 of the USH2A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230570 SCV003928763 pathogenic Usher syndrome 2023-04-26 criteria provided, single submitter clinical testing Variant summary: USH2A c.9258+1G>T 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: Three predict the variant abolishes the canonical 5' splicing donor site. However, to our knowledge these predictions have yet to be confirmed by functional studies. The variant was absent in 250118 control chromosomes (gnomAD). c.9258+1G>T has been reported in the literature in individuals affected with retinitis pigmentosa (example: Koyanagi_2019, Martin-Merida_2019, Kim_2021, and Ma_2021). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 31213501, 30902645, 33946315, 33691693). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV003446318 SCV004172047 likely pathogenic Retinitis pigmentosa 39 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003446317 SCV004172048 likely pathogenic Usher syndrome type 2A 2023-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV003446318 SCV004208365 likely pathogenic Retinitis pigmentosa 39 2023-12-02 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001075805 SCV004707912 pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research

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