Submissions for variant NM_000742.4(CHRNA2):c.745G>A (p.Ala249Thr)

gnomAD frequency: 0.00029  dbSNP: rs77710085

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000711162	SCV000240422	benign	not provided	2020-12-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000407778	SCV000473190	benign	Autosomal dominant nocturnal frontal lobe epilepsy 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081783	SCV000562073	likely benign	Autosomal dominant nocturnal frontal lobe epilepsy	2024-01-21	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000711162	SCV000702786	uncertain significance	not provided	2016-11-22	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711162	SCV000841492	benign	not provided	2018-03-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381622	SCV002674662	benign	Inborn genetic diseases	2019-01-08	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
PreventionGenetics, part of Exact Sciences	RCV003967466	SCV004777066	likely benign	CHRNA2-related disorder	2020-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).