Submissions for variant NM_000834.5(GRIN2B):c.2459G>A (p.Gly820Glu)

dbSNP: rs797044849

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000704324	SCV000833269	pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2020-01-27	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with clinical features of GRIN2B-related conditions (PMID: 25356899, 30440138). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 820 of the GRIN2B protein (p.Gly820Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant has been reported to affect GRIN2B protein function (PMID: 29681796, 30217972). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly820 amino acid residue in GRIN2B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28377535, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172338	SCV001335377	likely pathogenic	Intellectual disability, autosomal dominant 6	2017-04-04	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
GeneDx	RCV001555980	SCV001777480	pathogenic	not provided	2018-09-18	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29681796, 28377535, 30440138, 30217972, 27818011, 25356899)
Mendelics	RCV001172338	SCV002516519	pathogenic	Intellectual disability, autosomal dominant 6	2022-05-04	criteria provided, single submitter	clinical testing
GenomeConnect - Simons Searchlight	RCV001265384	SCV001443509	pathogenic	Complex neurodevelopmental disorder	2018-08-27	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-08-27 and interpreted as Pathogenic. Variant was initially reported on 2016-10-05 by GTR ID of laboratory name Radbound UMC. The reporting laboratory might also submit to ClinVar.
PreventionGenetics, part of Exact Sciences	RCV004723112	SCV005336722	pathogenic	GRIN2B-related disorder	2024-07-20	no assertion criteria provided	clinical testing	The GRIN2B c.2459G>A variant is predicted to result in the amino acid substitution p.Gly820Glu. This variant has been reported as de novo in multiple individuals with intellectual disability or epilepsy (see for example - Hamdan et al. 2014. PubMed ID: 25356899; Platzer et al. 2017. PubMed ID: 28377535; Table S2, McKnight et al. 2021. PubMed ID: 34926809). This variant has not been reported in a large population database, indicating this variant is rare. This variant has been interpreted as likely pathogenic/pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/580700/). This variant is interpreted as pathogenic.