rs12193068

chr6-101654362-A-C

Variant summary

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

The NM_021956.5(GRIK2):c.542-22261A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,184 control chromosomes in the GnomAD database, including 448 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 0.068 (448 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.542-22261A>C		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.542-22261A>C		intron_variant		5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10414 AN: 152066 Hom.: 448 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0219

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0685 AC: 10420 AN: 152184 Hom.: 448 Cov.: 32 AF XY: 0.0672 AC XY: 5001 AN XY: 74406

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0840 Hom.: 435

Bravo AF: 0.0659

Asia WGS AF: 0.0480 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.8
Dann	Benign	0.63

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: rs12193068; hg19: chr6-102102237;