Submissions for variant NM_206933.4(USH2A):c.7493del (p.Ser2498fs)

dbSNP: rs1553274448

Total submissions: 6

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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001234813	SCV001407473	pathogenic	not provided	2023-12-11	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. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal 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). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV003453296	SCV004183244	likely pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000680438	SCV004183245	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003453296	SCV004208372	pathogenic	Retinitis pigmentosa 39	2023-07-27	criteria provided, single submitter	clinical testing