ClinVar Miner

Submissions for variant NM_000748.3(CHRNB2):c.910A>G (p.Thr304Ala)

gnomAD frequency: 0.00001  dbSNP: rs780962241
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186993 SCV000240566 uncertain significance not provided 2018-07-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNB2 gene. The T304A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 1/15304 (0.007%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The T304A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001852445 SCV002154490 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 304 of the CHRNB2 protein (p.Thr304Ala). This variant is present in population databases (rs780962241, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CHRNB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205073). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CHRNB2 protein function with a negative predictive value of 80%. 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.

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