rs2518344

Variant names:

• chr6-101327270-A-G
• rs2518344
• ENST00000421544.6:c.-293-71715A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-101327270-A-G
• chr6-101327270-A-T

Variant summary

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

The ENST00000421544.6(GRIK2):​c.-293-71715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,688 control chromosomes in the GnomAD database, including 30,449 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 0.62 (30449 hom., cov: 31)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 6 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: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

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

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421544.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000421544.6	TSL:1	c.-293-71715A>G		intron	N/A	ENSP00000397026.1	Q13002-1
	GRIK2	ENST00000682090.1		c.-293-71715A>G		intron	N/A	ENSP00000508130.1	Q13002-1
	GRIK2	ENST00000683774.1		n.233-13272A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93179 AN: 151570 Hom.: 30394 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.615 AC: 93298 AN: 151688 Hom.: 30449 Cov.: 31 AF XY: 0.620 AC XY: 45966 AN XY: 74146

African (AFR) AF: 0.819 AC: 33938 AN: 41420

American (AMR) AF: 0.548 AC: 8331 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3468

East Asian (EAS) AF: 0.872 AC: 4487 AN: 5148

South Asian (SAS) AF: 0.716 AC: 3445 AN: 4814

European-Finnish (FIN) AF: 0.545 AC: 5730 AN: 10508

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34063 AN: 67816

Other (OTH) AF: 0.563 AC: 1187 AN: 2108

Alfa AF: 0.551 Hom.: 12508

Bravo AF: 0.622

Asia WGS AF: 0.767 AC: 2658 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.82
PhyloP100		-0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2518344; hg19: chr6-101775146; COSMIC: COSV60257060;