Submissions for variant NM_001134407.3(GRIN2A):c.736C>A (p.Leu246Ile)

gnomAD frequency: 0.00021  dbSNP: rs555768104

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000733007	SCV000861016	uncertain significance	not provided	2018-05-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001120323	SCV001278802	benign	Landau-Kleffner syndrome	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.
Invitae	RCV001120323	SCV001400172	likely benign	Landau-Kleffner syndrome	2023-11-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282350	SCV002571901	uncertain significance	not specified	2022-08-09	criteria provided, single submitter	clinical testing	Variant summary: GRIN2A c.736C>A (p.Leu246Ile) results in a conservative amino acid change located in the receptor, ligand binding region (IPR001828) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 250922 control chromosomes, predominantly at a frequency of 0.00074 within the African or African-American subpopulation in the gnomAD database. To our knowledge, no occurrence of c.736C>A in individuals affected with GRIN2A-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Two classified the variant as benign (n=1)/likely benign (n=1) and one classified it as VUS. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003908048	SCV004725318	likely benign	GRIN2A-related condition	2023-05-22	criteria provided, single submitter	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).