6-102018522-C-T

Variant summary

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

The NM_021956.5(GRIK2):c.2086-16819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,874 control chromosomes in the GnomAD database, including 5,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.27 (5987 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0480

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.2086-16819C>T		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.2086-16819C>T		intron_variant		5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41217 AN: 151756 Hom.: 5986 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.271 AC: 41227 AN: 151874 Hom.: 5987 Cov.: 32 AF XY: 0.274 AC XY: 20301 AN XY: 74208

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.268

Alfa AF: 0.297 Hom.: 3493

Bravo AF: 0.268

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

association, no assertion criteria provided

case-control

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Nov 02, 2015

The frequency of the homozygous SNP genotype was higher in the oral cancer patients in comparison to controls, implying the role of this genotype in predisposition of oral cancer while the heterozygous genotype had a higher frequency in the controls indicating decreased risk to oral cancer. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.89
Dann	Benign	0.14

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: rs1335022; hg19: chr6-102466397; COSMIC: COSV59767090;