rs12207601

Positions:

• chr6-101907992-A-G

Variant summary

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

The NM_021956.5(GRIK2):​c.1749-16609A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 151,530 control chromosomes in the GnomAD database, including 788 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 0.086 (788 hom., cov: 31)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.1749-16609A>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.1749-16609A>G		intron_variant		5	NM_021956.5	ENSP00000358130	P4

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13081 AN: 151412 Hom.: 789 Cov.: 31

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.0409

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0863 AC: 13079 AN: 151530 Hom.: 788 Cov.: 31 AF XY: 0.0839 AC XY: 6215 AN XY: 74044

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.000973

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.111

Alfa AF: 0.122 Hom.: 772

Bravo AF: 0.0827

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.49

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: rs12207601; hg19: chr6-102355867;