ENST00000421544.6:c.-293-29852T>C

Variant names:

• chr6-101369133-T-C
• rs10485266
• ENST00000421544.6:c.-293-29852T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder with impaired language and ataxia and with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000421544.6	c.-293-29852T>C		intron_variant	Intron 3 of 18	1		ENSP00000397026.1
GRIK2	ENST00000682090.1	c.-293-29852T>C		intron_variant	Intron 3 of 18			ENSP00000508130.1
GRIK2	ENST00000683774.1	n.348+28476T>C		intron_variant	Intron 5 of 16

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

African (AFR) AF: 0.00809 AC: 336 AN: 41552

American (AMR) AF: 0.0578 AC: 878 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3464

East Asian (EAS) AF: 0.153 AC: 792 AN: 5168

South Asian (SAS) AF: 0.0836 AC: 403 AN: 4822

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10602

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0330 AC: 2238 AN: 67844

Other (OTH) AF: 0.0466 AC: 98 AN: 2102

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
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs10485266; hg19: chr6-101817009;