rs2247218

Positions:

• chr6-101518677-T-C

Variant summary

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

The NM_021956.5(GRIK2):​c.116-103272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,054 control chromosomes in the GnomAD database, including 5,577 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 (5577 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.116-103272T>C		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.116-103272T>C		intron_variant		5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39147 AN: 151934 Hom.: 5567 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.258 AC: 39184 AN: 152054 Hom.: 5577 Cov.: 32 AF XY: 0.262 AC XY: 19445 AN XY: 74300

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.274

Alfa AF: 0.295 Hom.: 9014

Bravo AF: 0.250

Asia WGS AF: 0.205 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.62

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: rs2247218; hg19: chr6-101966553; COSMIC: COSV59721915;