rs2786251

Positions:

• chr6-101686147-C-G
• chr6-101686147-C-T

Variant summary

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

The NM_021956.5(GRIK2):​c.778-33C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,574,708 control chromosomes in the GnomAD database, including 69,367 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 0.38 (13502 hom., cov: 32)
  • Exomes 𝑓: 0.26 (55865 hom.)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.778-33C>G		intron_variant		ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.778-33C>G		intron_variant		5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57647 AN: 151756 Hom.: 13473 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.345

GnomAD3 exomes AF: 0.330 AC: 79437 AN: 241012 Hom.: 15053 AF XY: 0.320 AC XY: 41688 AN XY: 130394

Gnomad AFR exome AF: 0.659

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.493

Gnomad SAS exome AF: 0.377

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.264 AC: 375342 AN: 1422836 Hom.: 55865 Cov.: 24 AF XY: 0.266 AC XY: 188285 AN XY: 707580

Gnomad4 AFR exome AF: 0.657

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.380 AC: 57732 AN: 151872 Hom.: 13502 Cov.: 32 AF XY: 0.384 AC XY: 28498 AN XY: 74214

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.347

Alfa AF: 0.315 Hom.: 1658

Bravo AF: 0.399

Asia WGS AF: 0.483 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.54

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: rs2786251; hg19: chr6-102134022; COSMIC: COSV59775755;