6-101278887-A-G

Variant names:

• chr6-101278887-A-G
• rs589469
• ENST00000421544.6:c.-294+34231A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000421544.6(GRIK2):​c.-294+34231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,090 control chromosomes in the GnomAD database, including 2,681 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 0.18 (2681 hom., cov: 32)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815
• Publications: 2 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: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

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

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421544.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000421544.6	TSL:1	c.-294+34231A>G		intron	N/A	ENSP00000397026.1	Q13002-1
	GRIK2	ENST00000682090.1		c.-294+34231A>G		intron	N/A	ENSP00000508130.1	Q13002-1
	GRIK2	ENST00000683774.1		n.232+34231A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28011 AN: 151972 Hom.: 2679 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.184 AC: 28024 AN: 152090 Hom.: 2681 Cov.: 32 AF XY: 0.185 AC XY: 13787 AN XY: 74358

African (AFR) AF: 0.146 AC: 6060 AN: 41514

American (AMR) AF: 0.150 AC: 2298 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3468

East Asian (EAS) AF: 0.151 AC: 780 AN: 5176

South Asian (SAS) AF: 0.178 AC: 858 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2629 AN: 10588

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14076 AN: 67934

Other (OTH) AF: 0.169 AC: 356 AN: 2110

Alfa AF: 0.138 Hom.: 328

Bravo AF: 0.176

Asia WGS AF: 0.171 AC: 597 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.80
PhyloP100		0.81

Splicing

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

Other links and lift over

dbSNP: rs589469; hg19: chr6-101726763;