rs2058878

Variant names:

• chr12-13800184-T-A
• rs2058878
• NM_000834.5:c.412-46269A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-13800184-T-A
• chr12-13800184-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000834.5(GRIN2B):​c.412-46269A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,908 control chromosomes in the GnomAD database, including 14,932 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14932 hom., cov: 31)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 14 publications found

Genes affected

GRIN2B (HGNC:4586): (glutamate ionotropic receptor NMDA type subunit 2B) This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]

GRIN2B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• developmental and epileptic encephalopathy, 27

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability, autosomal dominant 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.412-46269A>T		intron_variant	Intron 3 of 13	ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.412-46269A>T		intron_variant	Intron 3 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.3	c.412-46269A>T		intron_variant	Intron 4 of 14	5		ENSP00000486677.3
GRIN2B	ENST00000714048.1	n.412-46269A>T		intron_variant	Intron 3 of 12			ENSP00000519339.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64628 AN: 151790 Hom.: 14927 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64669 AN: 151908 Hom.: 14932 Cov.: 31 AF XY: 0.421 AC XY: 31228 AN XY: 74214

African (AFR) AF: 0.254 AC: 10511 AN: 41434

American (AMR) AF: 0.431 AC: 6575 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1927 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1368 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2169 AN: 4810

European-Finnish (FIN) AF: 0.432 AC: 4552 AN: 10544

Middle Eastern (MID) AF: 0.479 AC: 138 AN: 288

European-Non Finnish (NFE) AF: 0.531 AC: 36050 AN: 67928

Other (OTH) AF: 0.473 AC: 996 AN: 2106

Alfa AF: 0.261 Hom.: 591

Bravo AF: 0.417

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.53
DANN	Benign	0.84
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2058878; hg19: chr12-13953118;