ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.4645C>T (p.Arg1549Ter) (rs199679165)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000605510 SCV000710864 pathogenic Rare genetic deafness 2017-08-15 criteria provided, single submitter clinical testing The p.Arg1549X variant in USH2A has been previously reported in over 10 individu als with Usher syndrome, most of whom were homozygous or compound heterozygous w ith a second pathogenic USH2A variant (Baux 2007, Bonnet 2016, Garcia-Garcia 201 1, Le Quesne Stabej 2012, Maranhao 2015, McGee 2010, Sandberg 2008, Zhao 2015). This variant has been identified in 2/111610 European chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs199679 165). Although this variant has been seen in the general population, its frequen cy is low enough to be consistent with a carrier frequency for autosomal recessi ve Usher syndrome. This nonsense variant leads to a premature termination codon at position 1549, which is predicted to lead to a truncated or absent protein. L oss of function of the USH2A gene is an established disease mechanism in autosom al recessive Usher syndrome. In summary, this variant meets criteria to be clas sified as pathogenic for autosomal recessive Usher syndrome, based on the previo usly reported individuals with Usher syndrome, a low frequency in the general po pulation, and predicted impact to the protein.
Counsyl RCV000669125 SCV000793839 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-09-11 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV001002689 SCV001156369 pathogenic Usher syndrome, type 2A 2019-02-01 criteria provided, single submitter clinical testing
Invitae RCV001208453 SCV001379842 pathogenic not provided 2020-08-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1549*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs199679165, ExAC 0.02%). This variant has been observed in individuals affected with Usher syndrome or retinitis pigmentosa (PMID: 28559085, 29899460, 26352687). ClinVar contains an entry for this variant (Variation ID: 504513). 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.
Natera, Inc. RCV001002689 SCV001462264 pathogenic Usher syndrome, type 2A 2020-09-16 no assertion criteria provided clinical testing
Genomics England Pilot Project,Genomics England RCV001002689 SCV001760018 pathogenic Usher syndrome, type 2A no assertion criteria provided clinical testing

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