rs10772692

Variant names:

• chr12-13568214-A-C
• rs10772692
• NM_000834.5:c.2360-951T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-13568214-A-C
• chr12-13568214-A-G
• chr12-13568214-A-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.2360-951T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,904 control chromosomes in the GnomAD database, including 16,010 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 0.44 (16010 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.2360-951T>G		intron_variant	Intron 12 of 13	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.2360-951T>G		intron_variant	Intron 13 of 14		NP_001400921.1
GRIN2B	XM_005253351.3	c.146-951T>G		intron_variant	Intron 2 of 3		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.2360-951T>G		intron_variant	Intron 12 of 13	1	NM_000834.5	ENSP00000477455.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66084 AN: 151786 Hom.: 16004 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.435 AC: 66112 AN: 151904 Hom.: 16010 Cov.: 32 AF XY: 0.431 AC XY: 31958 AN XY: 74184

African (AFR) AF: 0.215 AC: 8918 AN: 41488

American (AMR) AF: 0.510 AC: 7790 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1891 AN: 3466

East Asian (EAS) AF: 0.302 AC: 1537 AN: 5086

South Asian (SAS) AF: 0.367 AC: 1764 AN: 4804

European-Finnish (FIN) AF: 0.448 AC: 4721 AN: 10540

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37850 AN: 67942

Other (OTH) AF: 0.482 AC: 1017 AN: 2110

Alfa AF: 0.510 Hom.: 25669

Bravo AF: 0.432

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.56
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: rs10772692; hg19: chr12-13721148;