rs589469

Positions:

• chr6-101278887-A-G
• chr6-101278887-A-T

Variant summary

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

The ENST00000421544.6(GRIK2):​c.-294+34231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,090 control chromosomes in the GnomAD database, including 2,681 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 0.18 (2681 hom., cov: 32)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000421544.6	c.-294+34231A>G		intron_variant		1		ENSP00000397026	P4
GRIK2	ENST00000682090.1	c.-294+34231A>G		intron_variant				ENSP00000508130	P4
GRIK2	ENST00000683774.1	n.232+34231A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28011 AN: 151972 Hom.: 2679 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.184 AC: 28024 AN: 152090 Hom.: 2681 Cov.: 32 AF XY: 0.185 AC XY: 13787 AN XY: 74358

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.169

Alfa AF: 0.137 Hom.: 315

Bravo AF: 0.176

Asia WGS AF: 0.171 AC: 597 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs589469; hg19: chr6-101726763;