chr6-101327270-A-G

Position:

• chr6-101327270-A-G

Variant summary

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

The ENST00000421544.6(GRIK2):​c.-293-71715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,688 control chromosomes in the GnomAD database, including 30,449 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 0.62 (30449 hom., cov: 31)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 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.-293-71715A>G		intron_variant		1		ENSP00000397026	P4
GRIK2	ENST00000682090.1	c.-293-71715A>G		intron_variant				ENSP00000508130	P4
GRIK2	ENST00000683774.1	n.233-13272A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93179 AN: 151570 Hom.: 30394 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.615 AC: 93298 AN: 151688 Hom.: 30449 Cov.: 31 AF XY: 0.620 AC XY: 45966 AN XY: 74146

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.563

Alfa AF: 0.553 Hom.: 11216

Bravo AF: 0.622

Asia WGS AF: 0.767 AC: 2658 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2518344; hg19: chr6-101775146; COSMIC: COSV60257060;