rs2247215

Variant names:

• chr6-101518578-A-G
• rs2247215
• NM_021956.5:c.116-103371A>G

Variant summary

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

The ENST00000369134.9(GRIK2):​c.116-103371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,008 control chromosomes in the GnomAD database, including 5,633 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 0.26 (5633 hom., cov: 32)
• Consequence: GRIK2 ENST00000369134.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369134.9. 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.116-103371A>G		intron	N/A	NP_068775.1
	GRIK2	NM_001166247.1		c.116-103371A>G		intron	N/A	NP_001159719.1
	GRIK2	NM_175768.3		c.116-103371A>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.116-103371A>G		intron	N/A	ENSP00000358130.6
	GRIK2	ENST00000421544.6	TSL:1	c.116-103371A>G		intron	N/A	ENSP00000397026.1
	GRIK2	ENST00000369138.5	TSL:1	c.116-103371A>G		intron	N/A	ENSP00000358134.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39265 AN: 151888 Hom.: 5623 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.259 AC: 39300 AN: 152008 Hom.: 5633 Cov.: 32 AF XY: 0.262 AC XY: 19486 AN XY: 74294

African (AFR) AF: 0.142 AC: 5882 AN: 41510

American (AMR) AF: 0.298 AC: 4544 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3470

East Asian (EAS) AF: 0.154 AC: 793 AN: 5156

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3984 AN: 10548

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20964 AN: 67958

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.280 Hom.: 9026

Bravo AF: 0.250

Asia WGS AF: 0.204 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.45
PhyloP100		1.3
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: rs2247215; hg19: chr6-101966454; COSMIC: COSV59721907;