Submissions for variant NM_206933.4(USH2A):c.11875_11876del (p.Gln3959fs)

dbSNP: rs779791079

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179599	SCV000231869	pathogenic	not provided	2014-10-08	criteria provided, single submitter	clinical testing
Counsyl	RCV000671027	SCV000795965	pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2017-11-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000179599	SCV001168547	pathogenic	not provided	2018-08-30	criteria provided, single submitter	clinical testing	The c.11875_11876delCA variant in the USH2A gene has been reported previously in association with Usher syndrome (Dreyer et al., 2008). The c.11875_11876delCA variant causes a frameshift starting with codon Glutamine 3959, changes this amino acid to an Asparagine residue, and creates a premature Stop codon at position 53 of the new reading frame, denoted p.Gln3959AsnfsX53. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.11875_11876delCA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.11875_11876delCA as a pathogenic variant.
Blueprint Genetics	RCV001073824	SCV001239388	pathogenic	Retinal dystrophy	2018-05-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000179599	SCV001418176	pathogenic	not provided	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln3959Asnfs*53) 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 (rs779791079, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of retinal dystrophy (PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 198318). For these reasons, this variant has been classified as Pathogenic.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376411	SCV001573539	pathogenic	Retinitis pigmentosa 39	2021-04-08	criteria provided, single submitter	research	The USH2A c.11875_11876del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP3. Based on this evidence we have classified this variant as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000671027	SCV002792884	likely pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2022-03-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001376411	SCV004182061	likely pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001826918	SCV004182062	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001376411	SCV004208129	pathogenic	Retinitis pigmentosa 39	2024-03-04	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505154	SCV000598771	pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV001826918	SCV002088319	pathogenic	Usher syndrome type 2A	2020-09-01	no assertion criteria provided	clinical testing