ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.202C>T (p.Arg68Trp) (rs376970816)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186888 SCV000240459 uncertain significance not provided 2018-11-20 criteria provided, single submitter clinical testing The R68W variant in the CHRNA2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R68W variant is observed in 6/9848 (0.061%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). The R68W 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. However, this amino acid substitution does not occur within the second transmembrane domain of the protein, where the majority of pathogenic missense variants have been identified (Kurahashi and Hirose, 2015). We interpret R68W as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000291878 SCV000473199 benign Epilepsy, nocturnal frontal lobe, type 4 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics RCV000720058 SCV000850934 uncertain significance Seizures 2016-02-24 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678788 SCV000804968 uncertain significance myoclonic epilepsy 2016-09-28 no assertion criteria provided clinical testing

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