Submissions for variant NM_206933.4(USH2A):c.100C>T (p.Arg34Ter)

dbSNP: rs772808534

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000673031	SCV000798196	pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2018-03-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001039961	SCV001203513	pathogenic	not provided	2023-12-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg34*) 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 (rs772808534, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Usher syndrome or retinitis pigmentosa (PMID: 10909849, 15823922, 28041643). ClinVar contains an entry for this variant (Variation ID: 438000). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001039961	SCV001447949	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376313	SCV001573415	likely pathogenic	Retinitis pigmentosa 39	2021-04-08	criteria provided, single submitter	research	The USH2A c.100C>T 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. Based on this evidence we have classified this variant as Likely Pathogenic.
Genome-Nilou Lab	RCV001376313	SCV004183020	likely pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001273815	SCV004183021	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001376313	SCV004208236	pathogenic	Retinitis pigmentosa 39	2023-11-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479142	SCV004223235	pathogenic	Usher syndrome	2023-11-28	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.100C>T (p.Arg34X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250392 control chromosomes. c.100C>T has been reported in the literature in individuals affected with Usher Syndrome (e.g. Dreyer_2008). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. The following publication have been ascertained in the context of this evaluation (PMID: 18273898). All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx	RCV001039961	SCV005201533	pathogenic	not provided	2024-01-16	criteria provided, single submitter	clinical testing	Nonsense 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10909849, 28041643, 32581362, 32467589, 32675063, 36011334, 31964843, 32566994, 36110214, 29953849, 31266775, 37217489, 36819107, 25333064, 32995707, 16098008, 26338283, 35457016, 29912909, 35076463, 31429209, 34906470, 34948090, 22135276, 36460718, 19683999, 35665479, 15823922)
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504668	SCV000598760	pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV001273815	SCV001457335	pathogenic	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing