ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.10699del (p.Gln3566_Leu3567insTer)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089579 SCV001244814 pathogenic Usher syndrome, type 2A 2018-05-29 criteria provided, single submitter clinical testing A heterozygous nonsense variant, NM_206933.2(USH2A):c.10699delC, has been identified in exon 54 of 72 of the USH2A gene. The variant is predicted to result in a premature stop codon at position 3567 of the protein (NP_996816.2(USH2A):p.(Leu3567*)). This variant is predicted to result in loss of protein function either through truncation (including the loss of multiple domains) or nonsense-mediated decay. The variant is absent in population databases (gnomAD). It has not been previously reported in clinical cases however, multiple truncating variants (upstream and downstream) have previously been reported as pathogenic (ClinVar). Based on the information available at the time of curation and in conjunction with the c.2299delG variant, this variant has been classified as PATHOGENIC.NB: This variant has been reclassified as pathogenic due to confirmed compound heterozygous inheritance, consistent with Usher syndrome.
Invitae RCV001389327 SCV001590652 pathogenic not provided 2020-03-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu3567*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Usher syndrome (PMID: 30073356). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). For these reasons, this variant has been classified as Pathogenic.
DBGen Ocular Genomics RCV001593259 SCV001816034 pathogenic Retinitis pigmentosa 39 2021-06-28 criteria provided, single submitter clinical testing

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