rs513216

Positions:

• chr6-101611016-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021956.5(GRIK2):​c.116-10933C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,310 control chromosomes in the GnomAD database, including 14,147 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 0.41 (14147 hom., cov: 31)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5	c.116-10933C>T		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9	c.116-10933C>T		intron_variant		5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61633 AN: 151192 Hom.: 14114 Cov.: 31

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.408 AC: 61716 AN: 151310 Hom.: 14147 Cov.: 31 AF XY: 0.408 AC XY: 30140 AN XY: 73902

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.384

Alfa AF: 0.316 Hom.: 10813

Bravo AF: 0.414

Asia WGS AF: 0.543 AC: 1886 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.53

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: rs513216; hg19: chr6-102058891;