ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1644+5G>C

dbSNP: rs1558036810
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001073562 SCV001239113 uncertain significance Retinal dystrophy 2019-06-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003396731 SCV004121937 uncertain significance not specified 2023-10-19 criteria provided, single submitter clinical testing Variant summary: USH2A c.1644+5G>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a canonical 5' splicing donor site. Two predict the variant weakens a canonical 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250896 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1644+5G>C has been reported in the literature in an individual who underwent whole-genome sequencing analysis ( Turro_2020). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32581362). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV003446606 SCV004172202 uncertain significance Retinitis pigmentosa 39 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003446605 SCV004172203 uncertain significance Usher syndrome type 2A 2023-04-11 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003446605 SCV005400931 uncertain significance Usher syndrome type 2A criteria provided, single submitter clinical testing The observed splice c.1644+5G>C variant in USH2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1644+5G>C variant is present with allele frequency of 0.0004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. The SpliceAI predicts a score of 0.94 (Damaging) for this variant. Additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as a Variant of Uncertain Significance.

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