rs1806205

Variant names:

• chr12-13566469-G-C
• rs1806205
• NM_000834.5:c.2598+556C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-13566469-G-C
• chr12-13566469-G-T

Variant summary

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

The NM_000834.5(GRIN2B):​c.2598+556C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,038 control chromosomes in the GnomAD database, including 6,455 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 0.27 (6455 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.2598+556C>G		intron_variant	Intron 13 of 13	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.2598+556C>G		intron_variant	Intron 14 of 14		NP_001400921.1
GRIN2B	XM_005253351.3	c.384+556C>G		intron_variant	Intron 3 of 3		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.2598+556C>G		intron_variant	Intron 13 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.3	c.2598+556C>G		intron_variant	Intron 14 of 14	5		ENSP00000486677.3
GRIN2B	ENST00000637214.1	c.69+42134C>G		intron_variant	Intron 1 of 1	5		ENSP00000489997.1
GRIN2B	ENST00000714048.1	n.*403+556C>G		intron_variant	Intron 12 of 12			ENSP00000519339.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41733 AN: 151920 Hom.: 6450 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.275 AC: 41759 AN: 152038 Hom.: 6455 Cov.: 32 AF XY: 0.284 AC XY: 21126 AN XY: 74310

African (AFR) AF: 0.125 AC: 5189 AN: 41506

American (AMR) AF: 0.310 AC: 4735 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3468

East Asian (EAS) AF: 0.513 AC: 2651 AN: 5166

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4820

European-Finnish (FIN) AF: 0.389 AC: 4096 AN: 10534

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20526 AN: 67950

Other (OTH) AF: 0.300 AC: 634 AN: 2112

Alfa AF: 0.279 Hom.: 779

Bravo AF: 0.263

Asia WGS AF: 0.472 AC: 1635 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		0.50
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: rs1806205; hg19: chr12-13719403;