NM_021956.5:c.116-42892T>G

Variant names:

• chr6-101579057-T-G
• rs487083
• NM_021956.5:c.116-42892T>G

Variant summary

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

The NM_021956.5(GRIK2):​c.116-42892T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,996 control chromosomes in the GnomAD database, including 1,301 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 0.11 (1301 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 5 publications found

Genes affected

GRIK2 (HGNC:4580): (glutamate ionotropic receptor kainate type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]

GRIK2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder with impaired language and ataxia and with or without seizures

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

  Inheritance: AR 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	NM_021956.5	MANE Select	c.116-42892T>G		intron	N/A	NP_068775.1
	GRIK2	NM_001166247.1		c.116-42892T>G		intron	N/A	NP_001159719.1
	GRIK2	NM_175768.3		c.116-42892T>G		intron	N/A	NP_786944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000369134.9	TSL:5 MANE Select	c.116-42892T>G		intron	N/A	ENSP00000358130.6
	GRIK2	ENST00000421544.6	TSL:1	c.116-42892T>G		intron	N/A	ENSP00000397026.1
	GRIK2	ENST00000369138.5	TSL:1	c.116-42892T>G		intron	N/A	ENSP00000358134.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16781 AN: 151880 Hom.: 1293 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.111 AC: 16832 AN: 151996 Hom.: 1301 Cov.: 32 AF XY: 0.111 AC XY: 8280 AN XY: 74276

African (AFR) AF: 0.213 AC: 8820 AN: 41422

American (AMR) AF: 0.0614 AC: 937 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3464

East Asian (EAS) AF: 0.0483 AC: 249 AN: 5160

South Asian (SAS) AF: 0.117 AC: 564 AN: 4820

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10578

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4808 AN: 67984

Other (OTH) AF: 0.0891 AC: 188 AN: 2110

Alfa AF: 0.0776 Hom.: 936

Bravo AF: 0.111

Asia WGS AF: 0.0970 AC: 338 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.12
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: rs487083; hg19: chr6-102026932;