ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.545_546del (p.Lys182fs)

dbSNP: rs780779563
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Total submissions: 8
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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
Labcorp Genetics (formerly Invitae), Labcorp RCV001008088 SCV001591300 pathogenic not provided 2024-03-09 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. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal 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). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV003453346 SCV004182973 pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001829876 SCV004182974 pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003453346 SCV005055778 pathogenic Retinitis pigmentosa 39 2023-11-21 criteria provided, single submitter clinical testing
Natera, Inc. RCV001829876 SCV002094026 pathogenic Usher syndrome type 2A 2021-08-23 no assertion criteria provided clinical testing

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