ClinVar Miner

Submissions for variant NM_007123.5(USH2A):c.545_546del (p.Lys182fs) (rs780779563)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672318 SCV000797415 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2018-01-24 criteria provided, single submitter clinical testing
GeneDx RCV001008088 SCV001167833 pathogenic not provided 2018-11-02 criteria provided, single submitter clinical testing The c.545_546delAA variant in the USH2A gene has been reported previously in association with autosomal recessive Usher syndrome type II (Sayedahmadi et al., 2004; Hartel et al., 2016). In addition, the c.545_546delAA variant has been reported in an individual with retinitis pigmentosa who also had another frameshift variant in the USH2A gene (Sandberg et al., 2008). The c.545_546delAA variant causes a frameshift starting with codon Lysine 182, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 33 of the new reading frame, denoted p.Lys182ArgfsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.545_546delAA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.545_546delAA as a pathogenic variant.
Blueprint Genetics RCV001073226 SCV001238762 pathogenic Retinal dystrophy 2018-08-07 criteria provided, single submitter clinical testing
Invitae RCV001008088 SCV001591300 pathogenic not provided 2020-02-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys182Argfs*33) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs780779563, ExAC 0.002%). This variant has been observed in individual(s) with clinical features of Usher syndrome type II (PMID: 15325563, 18273898, 27318125). ClinVar contains an entry for this variant (Variation ID: 556324). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.