Submissions for variant NM_000742.4(CHRNA2):c.1434C>A (p.Asp478Glu)

gnomAD frequency: 0.00307  dbSNP: rs56344740

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124278	SCV000167705	benign	not specified	2013-05-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080927	SCV000285613	benign	Autosomal dominant nocturnal frontal lobe epilepsy	2024-01-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000768183	SCV000473182	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000419685	SCV000511714	likely benign	not provided	2016-09-01	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Eurofins Ntd Llc (ga)	RCV000124278	SCV000706592	likely benign	not specified	2017-03-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312821	SCV000848373	likely benign	Inborn genetic diseases	2018-09-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768183	SCV000898604	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 4	2021-03-30	criteria provided, single submitter	clinical testing	CHRNA2 NM_000742 exon 6 p.Asp478Glu (c.1434C>A): This variant has not been reported in the literature but is present in 0.5% (685/126322) of European alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs56344740). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID:136753). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Functional studies predict that this variant will impact the protein (Dash 2014 PMID:24950454). However, these studies may not accurately represent human biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Athena Diagnostics	RCV000419685	SCV001143532	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000768183	SCV001440254	likely benign	Autosomal dominant nocturnal frontal lobe epilepsy 4	2019-01-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000419685	SCV004164534	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	CHRNA2: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003905194	SCV004725787	benign	CHRNA2-related disorder	2019-04-12	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).