Submissions for variant NM_000834.5(GRIN2B):c.3076G>A (p.Gly1026Ser)

gnomAD frequency: 0.00011  dbSNP: rs201963596

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726884	SCV000241300	benign	not provided	2018-06-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27818011, 22986046, 22833210)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000471349	SCV000552120	benign	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2023-12-22	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726884	SCV000703861	uncertain significance	not provided	2016-12-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314720	SCV000849221	likely benign	Inborn genetic diseases	2024-01-12	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.
CeGaT Center for Human Genetics Tuebingen	RCV000726884	SCV001148650	likely benign	not provided	2020-07-01	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001781554	SCV002025703	likely benign	Developmental and epileptic encephalopathy, 27	2022-01-09	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000726884	SCV004235206	uncertain significance	not provided	2024-01-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003993873	SCV004813703	likely benign	not specified	2024-02-19	criteria provided, single submitter	clinical testing	Variant summary: GRIN2B c.3076G>A (p.Gly1026Ser) results in a non-conservative amino acid change located in the N-methyl D-aspartate receptor 2B3 C-terminus domain (IPR018884) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 251428 control chromosomes. c.3076G>A has been reported in the literature in at least one individual affected with autism spectrum disorder, without evidence for causation (e.g. Tarabeux_2011). This report does not provide unequivocal conclusions about association of the variant with Mental Retardation, Autosomal Dominant 6. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 22833210). ClinVar contains an entry for this variant (Variation ID: 205716). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004539739	SCV004760735	likely benign	GRIN2B-related disorder	2022-02-01	no assertion criteria provided	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).