ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.7493del (p.Ser2498fs) (rs1553274448)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670253 SCV000795086 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-10-26 criteria provided, single submitter clinical testing
GeneID Lab - Advanced Molecular Diagnostics RCV000680438 SCV000807809 likely pathogenic Usher syndrome, type 2A 2018-03-10 criteria provided, single submitter clinical testing This variant deletes one nucleotide resulting in an amino acid alteration, replacing a serine (S) with a methionine (M) at codon 2498 creating a premature stop signal in the new reading frame noted as p.S2498Mfs*30. The substitution is predicted to result in a non-functional USH2A protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the Clinical Variant Database (NCBI National Library of Medicine, NIH) or in population databases such as ExAC or 1000G. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant.
Invitae RCV001234813 SCV001407473 pathogenic not provided 2020-06-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser2498Metfs*30) 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 autosomal recessive retinitis pigmentosa or Usher syndrome type II (PMID: 18641288, 20507924). ClinVar contains an entry for this variant (Variation ID: 554589). 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.

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