ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.221C>T (p.Ala74Val)

dbSNP: rs759595350
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186858 SCV000240429 uncertain significance not provided 2020-03-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001370927 SCV001567474 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2022-03-09 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.003%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 204953). This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 74 of the CHRNA2 protein (p.Ala74Val).
PreventionGenetics, part of Exact Sciences RCV003416114 SCV004116117 uncertain significance CHRNA2-related disorder 2023-10-04 criteria provided, single submitter clinical testing The CHRNA2 c.221C>T variant is predicted to result in the amino acid substitution p.Ala74Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-27327351-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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