Submissions for variant NM_206933.4(USH2A):c.13112_13115del (p.Gln4371fs)

gnomAD frequency: 0.00001  dbSNP: rs768161313

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674880	SCV000800288	likely pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2018-05-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000734827	SCV000862999	pathogenic	not provided	2018-08-15	criteria provided, single submitter	clinical testing
Invitae	RCV000734827	SCV001222109	pathogenic	not provided	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln4371Argfs*19) 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 (rs768161313, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with USH2A-related conditions (PMID: 28894305; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 558585). For these reasons, this variant has been classified as Pathogenic.
3billion	RCV000985058	SCV002521878	pathogenic	Usher syndrome type 2A	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000558585 / PMID: 31674169 / 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
PreventionGenetics, part of Exact Sciences	RCV004535690	SCV004114419	pathogenic	USH2A-related disorder	2023-01-22	criteria provided, single submitter	clinical testing	The USH2A c.13112_13115delAAAT variant is predicted to result in a frameshift and premature protein termination (p.Gln4371Argfs*19). This variant has been previously reported in the compound heterozygous state in individuals with sensorineural hearing loss, retinitis pigmentosa/Usher syndrome type II (Sengillo et al. 2017. PubMed ID: 28894305; Lee et al. 2020. PubMed ID: 31674169; Gao et al. 2021. PubMed ID: 32188678; Zhu et al. 2021. PubMed ID: 32675063). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-215848137-CATTT-C). Frameshift variants in USH2A are expected to be pathogenic. This variant is interpreted as pathogenic.
Genome-Nilou Lab	RCV003223665	SCV004181909	likely pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000985058	SCV004181910	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003223665	SCV004208387	pathogenic	Retinitis pigmentosa 39	2024-02-13	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003889966	SCV004707250	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000985058	SCV001133000	likely pathogenic	Usher syndrome type 2A	2019-09-15	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000985058	SCV002088281	pathogenic	Usher syndrome type 2A	2020-09-30	no assertion criteria provided	clinical testing
OMIM	RCV003223665	SCV003841032	pathogenic	Retinitis pigmentosa 39	2023-04-17	no assertion criteria provided	literature only