Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002317569 | SCV000851088 | uncertain significance | Inborn genetic diseases | 2016-06-14 | criteria provided, single submitter | clinical testing | The p.S488L variant (also known as c.1463C>T), located in coding exon 5 of the CHRNA2 gene, results from a C to T substitution at nucleotide position 1463. The serine at codon 488 is replaced by leucine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001313435 | SCV001503932 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 488 of the CHRNA2 protein (p.Ser488Leu). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 589859). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Genetics and Genomic Medicine Centre, |
RCV004569411 | SCV004175116 | likely pathogenic | not provided | 2022-01-15 | no assertion criteria provided | clinical testing |