ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.380T>G (p.Phe127Cys)

dbSNP: rs777304017
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001979574 SCV002257046 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2021-12-02 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) performed at Invitae indicates that this missense variant is not expected to disrupt CHRNA2 protein function. This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. This variant is present in population databases (rs777304017, gnomAD 0.002%). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 127 of the CHRNA2 protein (p.Phe127Cys).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004699599 SCV005205012 uncertain significance not specified 2024-06-07 criteria provided, single submitter clinical testing Variant summary: CHRNA2 c.380T>G (p.Phe127Cys) results in a non-conservative amino acid change located in the neurotransmitter-gated ion-channel ligand-binding domain (IPR006202) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251488 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.380T>G in individuals affected with autosomal dominant nocturnal frontal lobe epilepsy 4 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1466288). Based on the evidence outlined above, the variant was classified as uncertain significance.

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