rs2518261

Variant names:

• chr6-101533902-T-C
• rs2518261
• NM_021956.5:c.116-88047T>C

Variant summary

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

The NM_021956.5(GRIK2):​c.116-88047T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,794 control chromosomes in the GnomAD database, including 24,814 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 0.57 (24814 hom., cov: 33)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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: 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	NM_021956.5	MANE Select	c.116-88047T>C		intron	N/A	NP_068775.1
	GRIK2	NM_001166247.1		c.116-88047T>C		intron	N/A	NP_001159719.1
	GRIK2	NM_175768.3		c.116-88047T>C		intron	N/A	NP_786944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000369134.9	TSL:5 MANE Select	c.116-88047T>C		intron	N/A	ENSP00000358130.6
	GRIK2	ENST00000421544.6	TSL:1	c.116-88047T>C		intron	N/A	ENSP00000397026.1
	GRIK2	ENST00000369138.5	TSL:1	c.116-88047T>C		intron	N/A	ENSP00000358134.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86332 AN: 151676 Hom.: 24786 Cov.: 33

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.569 AC: 86414 AN: 151794 Hom.: 24814 Cov.: 33 AF XY: 0.563 AC XY: 41760 AN XY: 74206

African (AFR) AF: 0.592 AC: 24496 AN: 41406

American (AMR) AF: 0.526 AC: 8000 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2181 AN: 3472

East Asian (EAS) AF: 0.565 AC: 2905 AN: 5138

South Asian (SAS) AF: 0.424 AC: 2050 AN: 4830

European-Finnish (FIN) AF: 0.529 AC: 5593 AN: 10564

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39376 AN: 67854

Other (OTH) AF: 0.574 AC: 1209 AN: 2106

Alfa AF: 0.579 Hom.: 11192

Bravo AF: 0.572

Asia WGS AF: 0.508 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2518261; hg19: chr6-101981778;