ClinVar Miner

Submissions for variant NM_014249.4(NR2E3):c.166G>A (p.Gly56Arg)

gnomAD frequency: 0.00001  dbSNP: rs121912631
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000286602 SCV000227426 pathogenic not provided 2015-05-18 criteria provided, single submitter clinical testing
UCLA Clinical Genomics Center, UCLA RCV000005871 SCV000255426 likely pathogenic Retinitis pigmentosa 37 2013-02-05 criteria provided, single submitter clinical testing
GeneDx RCV000286602 SCV000330651 pathogenic not provided 2016-07-22 criteria provided, single submitter clinical testing The G56R pathogenic variant in the NR2E3 gene has been reported previously in several families with autosomal dominant retinitis pigmentosa (adRP), with one study reporting this variant in 7/201 (3.5%) of families with adRP who were tested (Coppieters et al., 2007; Blanco-Kelly et al., 2016). This variant was not observed in approximately 6300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G56R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G56R as a pathogenic variant.
Invitae RCV000286602 SCV001205035 pathogenic not provided 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 56 of the NR2E3 protein (p.Gly56Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 17564971, 17982421, 19006237, 26910043). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5533). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NR2E3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NR2E3 function (PMID: 19006237, 19823680). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075751 SCV001241381 pathogenic Retinal dystrophy 2019-06-05 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000286602 SCV001447300 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000005871 SCV002526723 pathogenic Retinitis pigmentosa 37 2022-05-30 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PS1, PS4, PP1_STR, PS3_MOD, PM2_SUP
OMIM RCV000005871 SCV000026053 pathogenic Retinitis pigmentosa 37 2007-07-01 no assertion criteria provided literature only
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787628 SCV000926613 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV000005871 SCV002583439 pathogenic Retinitis pigmentosa 37 2022-05-02 no assertion criteria provided clinical testing

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