ClinVar Miner

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

gnomAD frequency: 0.00005  dbSNP: rs376970816
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186888 SCV000240459 uncertain significance not provided 2021-03-30 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Illumina Laboratory Services,Illumina RCV000291878 SCV000473199 benign Autosomal dominant nocturnal frontal lobe epilepsy 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 likely benign Seizure 2020-04-17 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV001373739 SCV001570471 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2020-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 68 of the CHRNA2 protein (p.Arg68Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs376970816, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CHRNA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 204982). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.
CeGaT Center for Human Genetics Tuebingen RCV000186888 SCV002063181 uncertain significance not provided 2021-11-01 criteria provided, single submitter clinical testing
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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