ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.7300+1G>C

gnomAD frequency: 0.00001  dbSNP: rs1343780391
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001377091 SCV001574324 likely pathogenic not provided 2020-07-28 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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). This sequence change affects a donor splice site in intron 38 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 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 disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222707 SCV002500108 likely pathogenic Usher syndrome 2022-03-04 criteria provided, single submitter clinical testing Variant summary: USH2A c.7300+1G>C alters a conserved nucleotide 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: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250514 control chromosomes. To our knowledge, no occurrence of c.7300+1G>C in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Genome-Nilou Lab RCV003446733 SCV004172083 likely pathogenic Usher syndrome type 2A 2023-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV003462944 SCV004206328 likely pathogenic Retinitis pigmentosa 39 2023-02-12 criteria provided, single submitter clinical testing

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