rs2247215

chr6-101518578-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021956.5(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 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.116-103371A>G		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.116-103371A>G		intron_variant		5	NM_021956.5	P4

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.275

Alfa AF: 0.264 Hom.: 722

Bravo AF: 0.250

Asia WGS AF: 0.204 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.2
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2247215; hg19: chr6-101966454; COSMIC: COSV59721907;