ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs768161313
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.