6-101226414-C-T

Position:

• chr6-101226414-C-T

Variant summary

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

The ENST00000421544.6(GRIK2):​c.-320-18216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,066 control chromosomes in the GnomAD database, including 44,637 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 0.76 (44637 hom., cov: 32)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

GRIK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107984041	XR_002956381.2	n.534-5256C>T		intron_variant
LOC107984041	XR_007059692.1	n.534-18216C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000421544.6	c.-320-18216C>T		intron_variant		1		ENSP00000397026.1
GRIK2	ENST00000682090.1	c.-320-18216C>T		intron_variant				ENSP00000508130.1
GRIK2	ENST00000683774.1	n.206-18216C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115896 AN: 151948 Hom.: 44606 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.763 AC: 115983 AN: 152066 Hom.: 44637 Cov.: 32 AF XY: 0.764 AC XY: 56814 AN XY: 74320

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.801

Alfa AF: 0.790 Hom.: 11292

Bravo AF: 0.755

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.95
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2797369; hg19: chr6-101674290;