ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.140C>T (p.Thr47Met) (rs74772771)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727343 SCV000240456 uncertain significance not provided 2018-02-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA2 gene. The T47M variant has been reported previously in two unrelated individuals with idiopathic generalized epilepsy; however, no additional information was provided (Klassen et al., 2011; Wei et al., 2017). The T47M 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, the T47M variant is observed in 111/126604 (0.1%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). 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). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001079768 SCV000551796 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2019-12-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727343 SCV000707719 uncertain significance not provided 2018-01-04 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000615228 SCV000743961 likely benign Epilepsy, nocturnal frontal lobe, type 4 2017-07-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000727343 SCV000892830 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing
Mendelics RCV000615228 SCV001137599 uncertain significance Epilepsy, nocturnal frontal lobe, type 4 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000615228 SCV001327005 benign Epilepsy, nocturnal frontal lobe, type 4 2018-01-12 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.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000615228 SCV000734602 likely benign Epilepsy, nocturnal frontal lobe, type 4 no assertion criteria provided clinical testing

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