Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001049200 | SCV001213239 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys425*) 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. This variant is present in population databases (rs530383631, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. This premature translational stop signal has been observed in at least one individual who was not affected with CHRNA2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 846007). 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. |
Ambry Genetics | RCV002374896 | SCV002684548 | uncertain significance | Inborn genetic diseases | 2017-08-02 | criteria provided, single submitter | clinical testing | The p.C425* variant (also known as c.1275T>A), located in coding exon 5 of the CHRNA2 gene, results from a T to A substitution at nucleotide position 1275. This changes the amino acid from a cysteine 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. |
Fulgent Genetics, |
RCV002505593 | SCV002816464 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy 4 | 2022-04-22 | criteria provided, single submitter | clinical testing |