ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.869C>T (p.Pro290Leu)

gnomAD frequency: 0.00004  dbSNP: rs767619637
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437020 SCV000535188 uncertain significance not provided 2018-11-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA2 gene. The P290L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P290L variant is observed on 11/33582 (0.03%) alleles from individuals of Latino background in large population cohorts, which is greater than expected for this disorder (Lek et al., 2016). The P290L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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). However, in silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001038713 SCV001202199 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2022-11-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002488973 SCV002775630 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 4 2021-09-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002522663 SCV003682118 likely benign Inborn genetic diseases 2021-07-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.