6-101398678-G-A

Position:

• chr6-101398678-G-A

Variant summary

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

The NM_021956.5(GRIK2):​c.-293-307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 215,342 control chromosomes in the GnomAD database, including 5,230 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 0.21 (4120 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1110 hom.)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.-293-307G>A		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.-293-307G>A		intron_variant		5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32575 AN: 151952 Hom.: 4108 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.175 AC: 11044 AN: 63272 Hom.: 1110 AF XY: 0.172 AC XY: 5568 AN XY: 32436

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.0807

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.214 AC: 32614 AN: 152070 Hom.: 4120 Cov.: 32 AF XY: 0.211 AC XY: 15687 AN XY: 74350

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.0950

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.159

Alfa AF: 0.214 Hom.: 554

Bravo AF: 0.213

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2852512; hg19: chr6-101846554; COSMIC: COSV59721548;