ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.4645C>T (p.Arg1549Ter) (rs199679165)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669125 SCV000793839 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-09-11 criteria provided, single submitter clinical testing
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, http://gnomad.broadinstitute.org/; 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.

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