Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001208620 | SCV001380019 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-05-20 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CHRNA2 protein function. ClinVar contains an entry for this variant (Variation ID: 939252). This missense change has been observed in at least one individual who was not affected with CHRNA2-related conditions (Invitae). This variant is present in population databases (rs56339365, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 355 of the CHRNA2 protein (p.Arg355Cys). |
New York Genome Center | RCV001263318 | SCV001441359 | uncertain significance | Seizure | 2020-01-31 | criteria provided, single submitter | clinical testing | The c.1063C>T, p.Arg355Cys missense variant in the CHRNA2 gene has not been reported in the available literature. The variant has a 0.0015% allele frequency in the gnomAD database (4 out of 250,686 heterozygous alleles), indicating this is a rare allele. In silico tools, support a deleterious effect on the gene or gene product. Based on the available evidence, the c.1063C>T, p.Arg355Cys missense variant in the CHRNA2 gene is classified as a variant of uncertain significance |