ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.1275T>A (p.Cys425Ter)

gnomAD frequency: 0.00003  dbSNP: rs530383631
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Total submissions: 3
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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, Fulgent Genetics RCV002505593 SCV002816464 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 4 2022-04-22 criteria provided, single submitter clinical testing

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