Submissions for variant NM_005045.4(RELN):c.139G>A (p.Glu47Lys)

gnomAD frequency: 0.00047  dbSNP: rs139648092

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000421637	SCV000113131	uncertain significance	not provided	2016-05-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000317927	SCV000465995	uncertain significance	Norman-Roberts syndrome	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000421637	SCV000510936	uncertain significance	not provided	2016-08-19	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Invitae	RCV000653007	SCV000774881	likely benign	Norman-Roberts syndrome; Familial temporal lobe epilepsy 7	2024-01-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764677	SCV000895807	uncertain significance	Epilepsy, familial temporal lobe, 1; Norman-Roberts syndrome; Familial temporal lobe epilepsy 7	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000421637	SCV001476809	uncertain significance	not provided	2020-07-24	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000317927	SCV002025769	uncertain significance	Norman-Roberts syndrome	2020-04-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002514433	SCV003526477	uncertain significance	Inborn genetic diseases	2020-11-04	criteria provided, single submitter	clinical testing	The c.139G>A (p.E47K) alteration is located in coding exon 1 of the RELN gene. This alteration results from a G to A substitution at nucleotide position 139, causing the glutamic acid (E) at amino acid position 47 to be replaced by a lysine (K). Based on data from the Genome Aggregation Database (gnomAD) database, the RELN c.139G>A alteration was observed in 0.03% (97/282290) of total alleles studied, with a frequency of 0.07% (88/128722) in the European (non-Finnish) subpopulation. In non-Finnish European cohort with Rolandic epilepsy, this variant was detected in two cases and one control (Bobbili, 2018). This amino acid position is well conserved in available vertebrate species. The p.E47K alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000317927	SCV003813837	uncertain significance	Norman-Roberts syndrome	2019-04-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000421637	SCV003929537	uncertain significance	not provided	2023-06-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV000421637	SCV004010705	uncertain significance	not provided	2023-04-01	criteria provided, single submitter	clinical testing
Bioinformatics Core, Luxembourg Center for Systems Biomedicine	RCV000656004	SCV000588280	pathogenic	Childhood epilepsy with centrotemporal spikes	2017-01-01	no assertion criteria provided	case-control	CAADphred>15