Submissions for variant NM_001134407.3(GRIN2A):c.2985G>A (p.Thr995=)

gnomAD frequency: 0.00001  dbSNP: rs781646325

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000614558	SCV000717470	likely benign	not specified	2017-03-22	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.
Invitae	RCV001060060	SCV001224721	uncertain significance	Landau-Kleffner syndrome	2022-02-04	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 508346). This variant is present in population databases (rs781646325, gnomAD 0.009%). This sequence change affects codon 995 of the GRIN2A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GRIN2A protein.
Illumina Laboratory Services, Illumina	RCV001060060	SCV001280511	uncertain significance	Landau-Kleffner 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.