ClinVar Miner

Submissions for variant NM_005654.6(NR2F1):c.1097G>A (p.Arg366His)

dbSNP: rs1753373048
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV001265635 SCV001443775 likely pathogenic Bosch-Boonstra-Schaaf optic atrophy syndrome 2020-11-19 criteria provided, single submitter clinical testing The variant c.1097G>A (p.(Arg366His)) in exon 3 of the NR2F1-gene is not found in known databases (ExAC or gnomAD), it affects a highly conserved nucleotide, a highly conserved amino acid and there is a small physicochemical difference between Arg and His. This variant is located within a protein domain and a mutational hotspot and has a pathogenic computational verdict based on 14 pathogenic predictions from BayesDel_addAF, DANN, DEOGEN2, EIGEN, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationAssessor, MutationTaster, PrimateAI, PolyPhen-2, REVEL and SIFT vs no benign predictions. This variant was found to be de novo in our patient. ACMG criteria used for classification: PM2, PM1, PM6, PP2, PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV003698856 SCV004455772 uncertain significance not provided 2023-09-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 366 of the NR2F1 protein (p.Arg366His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NR2F1-related conditions. ClinVar contains an entry for this variant (Variation ID: 984969). 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 NR2F1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV003698856 SCV005080116 uncertain significance not provided 2023-12-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26986877)

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