rs10485266

chr6-101369133-T-C

Variant summary

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

The ENST00000421544.6(GRIK2):c.-293-29852T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 151,962 control chromosomes in the GnomAD database, including 148 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 0.034 (148 hom., cov: 32)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000421544.6	c.-293-29852T>C		intron_variant		1		P4
GRIK2	ENST00000682090.1	c.-293-29852T>C		intron_variant				P4
GRIK2	ENST00000683774.1	n.348+28476T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5104 AN: 151844 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.00809

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0481

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

GnomAD4 genome AF: 0.0336 AC: 5104 AN: 151962 Hom.: 148 Cov.: 32 AF XY: 0.0345 AC XY: 2564 AN XY: 74274

Gnomad4 AFR AF: 0.00809

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0836

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0466

Alfa AF: 0.0318 Hom.: 15

Bravo AF: 0.0360

Asia WGS AF: 0.115 AC: 396 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.0
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10485266; hg19: chr6-101817009;