Submissions for variant NM_206933.4(USH2A):c.5877del (p.Ser1961fs)

dbSNP: rs727505343

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000824786	SCV000206616	pathogenic	Rare genetic deafness	2016-01-04	criteria provided, single submitter	clinical testing	The p.Ser1961fs variant in USH2A has been previously identified by our laborator y in one individual with hearing loss who also carried a second pathogenic USH2A variant (LMM unpublished data). It has also been identified in 1/8254 of Europe an American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS/); however, its frequency is low enough to be consistent with a recessive carrier frequency. The variant is predicted to cause a frameshift, whi ch alters the protein?s amino acid sequence beginning at position 1961 and leads to a premature termination codon 6 amino acids downstream. This alteration is t hen predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic for Usher syndrome in an auto somal recessive manner.
CeGaT Center for Human Genetics Tuebingen	RCV000487657	SCV000574819	pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	USH2A: PVS1, PM2
Eurofins Ntd Llc (ga)	RCV000487657	SCV000701901	pathogenic	not provided	2016-10-04	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, Institute for Ophthalmic Research	RCV001199802	SCV001162742	pathogenic	Usher syndrome type 2	2020-01-09	criteria provided, single submitter	research
Blueprint Genetics	RCV001074210	SCV001239783	likely pathogenic	Retinal dystrophy	2019-03-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000487657	SCV001779585	pathogenic	not provided	2021-02-02	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002498773	SCV002811107	likely pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2021-07-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000487657	SCV002987836	pathogenic	not provided	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1961Glnfs*6) 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 inherited retinal degeneration (PMID: 32531858). ClinVar contains an entry for this variant (Variation ID: 180092). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000412258	SCV004181749	likely pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000156895	SCV004181750	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000412258	SCV004208266	pathogenic	Retinitis pigmentosa 39	2023-09-13	criteria provided, single submitter	clinical testing
Counsyl	RCV000156895	SCV000487436	likely pathogenic	Usher syndrome type 2A	2016-07-22	no assertion criteria provided	clinical testing
Counsyl	RCV000412258	SCV000487437	likely pathogenic	Retinitis pigmentosa 39	2016-07-22	no assertion criteria provided	clinical testing