Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001732931 | SCV001982596 | pathogenic | not provided | 2023-02-21 | 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) |
| Illumina Laboratory Services, |
RCV003985104 | SCV004801616 | likely pathogenic | Bosch-Boonstra-Schaaf optic atrophy syndrome | 2018-08-27 | criteria provided, single submitter | clinical testing | The NR2F1 c.310G>A p.(Glu104Lys) missense variant has not, to our knowledge, been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 of the Genome Aggregation Database. The variant is located within the protein's zinc finger DNA binding domain, a common site of pathogenic missense variants (Bosch et al. 2014; Chen et al. 2016; Kaiwar et al. 2017; Martín-Hernández et al. 2018). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the available evidence the c.310G>A p.(Glu104Lys) variant is classified as likely pathogenic for Bosch-Boonstra-Schaaf optic atrophy syndrome. |
| Labcorp Genetics |
RCV001732931 | SCV005756988 | uncertain significance | not provided | 2024-06-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 104 of the NR2F1 protein (p.Glu104Lys). 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: 1300551). 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 with a positive predictive value of 80%. 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. |