rs2852618

Variant names:

• chr6-102062377-A-G
• rs2852618
• NM_021956.5:c.2563-5970A>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.2563-5970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 149,996 control chromosomes in the GnomAD database, including 13,613 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 0.42 (13613 hom., cov: 31)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 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.2563-5970A>G		intron	N/A	NP_068775.1
	GRIK2	NM_001166247.1		c.2563-3420A>G		intron	N/A	NP_001159719.1
	GRIK2	NM_175768.3		c.2563-1585A>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.2563-5970A>G		intron	N/A	ENSP00000358130.6
	GRIK2	ENST00000421544.6	TSL:1	c.2563-5970A>G		intron	N/A	ENSP00000397026.1
	GRIK2	ENST00000369138.5	TSL:1	c.2563-3420A>G		intron	N/A	ENSP00000358134.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 63407 AN: 149878 Hom.: 13614 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.423 AC: 63429 AN: 149996 Hom.: 13613 Cov.: 31 AF XY: 0.417 AC XY: 30599 AN XY: 73298

African (AFR) AF: 0.356 AC: 14703 AN: 41274

American (AMR) AF: 0.438 AC: 6563 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1489 AN: 3434

East Asian (EAS) AF: 0.351 AC: 1794 AN: 5116

South Asian (SAS) AF: 0.310 AC: 1490 AN: 4812

European-Finnish (FIN) AF: 0.426 AC: 4475 AN: 10502

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31309 AN: 66584

Other (OTH) AF: 0.431 AC: 896 AN: 2080

Alfa AF: 0.447 Hom.: 2476

Bravo AF: 0.426

Asia WGS AF: 0.312 AC: 1080 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.5
DANN	Benign	0.75
PhyloP100		-0.34
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: rs2852618; hg19: chr6-102510252; COSMIC: COSV59767275;