ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.5573-834A>G

gnomAD frequency: 0.00001  dbSNP: rs1558244152
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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 RCV001075747 SCV001241377 likely pathogenic Retinal dystrophy 2019-05-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001862631 SCV002229973 pathogenic not provided 2024-03-06 criteria provided, single submitter clinical testing This sequence change falls in intron 27 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with USH2A-related conditions (PMID: 26629787; Invitae). ClinVar contains an entry for this variant (Variation ID: 867167). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 26629787). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV003127624 SCV003802706 likely pathogenic Retinitis pigmentosa 39 2023-02-13 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003127624 SCV004172120 likely pathogenic Retinitis pigmentosa 39 2023-04-11 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004733154 SCV005361963 likely pathogenic USH2A-related disorder 2024-09-18 no assertion criteria provided clinical testing The USH2A c.5573-834A>G variant is predicted to interfere with splicing. This deep intronic variant is predicted to activate a cryptic splice acceptor site (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). A functional study using a minigene splicing assay confirmed this variant causes the inclusion of pseudoexons in the transcript (Liquori et al 2016. PubMed ID: 26629787). This variant has been reported along with a second USH2A variant in multiple individuals with Usher syndrome (Liquori et al. 2016. PubMed ID: 26629787; Table S1, Hufnagel et al. 2022. PubMed ID: 35266249; Reurink et al. 2023. PubMed ID: 36785559). This variant is reported in 0.0065% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic.

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