Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002322725 | SCV002609294 | uncertain significance | Inborn genetic diseases | 2017-10-27 | criteria provided, single submitter | clinical testing | The p.W377* variant (also known as c.1131G>A), located in coding exon 5 of the CHRNA2 gene, results from a G to A substitution at nucleotide position 1131. This changes the amino acid from a tryptophan to a stop codon within coding exon 5. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of CHRNA2 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003099266 | SCV003229984 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-03-12 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 1728522). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp377*) in the CHRNA2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CHRNA2 cause disease. |