ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.383G>A (p.Gly128Asp) (rs138682847)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000711161 SCV000230953 uncertain significance not provided 2015-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000186850 SCV000240421 uncertain significance not specified 2017-05-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA2 gene. The G128D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G128D variant is observed in 13/10404 (0.13%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G128D 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. However, this substitution occurs at a position that is not conserved. Additionally, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001080185 SCV000562067 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000711161 SCV000841491 likely benign not provided 2017-05-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000717606 SCV000848459 likely benign Seizures 2018-07-14 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;In silico models in agreement (benign)

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