ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7362+5G>A

gnomAD frequency: 0.00001  dbSNP: rs727502931
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000844693 SCV000197403 pathogenic Rare genetic deafness 2013-09-25 criteria provided, single submitter clinical testing The 7362+5G>A variant in CDH23 has been identified in three German individuals w ith Usher syndrome who were either homozygous or had a second variant in CDH23, and was not observed in at least 400 ethnically matched chromosomes (Bolz 2001, von Brederlow 2002, Glockle 2013). In addition, this variant is located in the c onserved 5' splice region, and functional analyses using RT-PCR reveal that the variant causes an in-frame skipping of exon 52 (Bolz 2001). In summary, this var iant meets our criteria to be classified as pathogenic (http://pcpgm.partners.or g/LMM) based upon its presence in individuals with Usher syndrome and its observ ed impact on splicing.
Labcorp Genetics (formerly Invitae), Labcorp RCV001851662 SCV002239179 pathogenic not provided 2024-02-04 criteria provided, single submitter clinical testing This sequence change falls in intron 52 of the CDH23 gene. It does not directly change the encoded amino acid sequence of the CDH23 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs727502931, gnomAD 0.01%). This variant has been observed in individual(s) with Usher syndrome (PMID: 11138009, 11857743, 23591405). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS51+5G>A. ClinVar contains an entry for this variant (Variation ID: 4918). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 52, but is expected to preserve the integrity of the reading-frame (PMID: 11138009). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000005200 SCV003918851 pathogenic Usher syndrome type 1D 2023-04-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV003472973 SCV004210664 pathogenic Pituitary adenoma 5, multiple types 2023-06-29 criteria provided, single submitter clinical testing
OMIM RCV000005200 SCV000025377 pathogenic Usher syndrome type 1D 2001-01-01 no assertion criteria provided literature only

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