rs2518224

Variant names:

• chr6-101458776-A-C
• rs2518224
• NM_021956.5:c.115+59384A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-101458776-A-C
• chr6-101458776-A-G

Variant summary

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

The NM_021956.5(GRIK2):​c.115+59384A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 152,220 control chromosomes in the GnomAD database, including 629 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 0.083 (629 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 12 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 (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.115+59384A>C		intron_variant	Intron 2 of 16	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.115+59384A>C		intron_variant	Intron 2 of 16	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12672 AN: 152102 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0848

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

GnomAD4 genome AF: 0.0833 AC: 12675 AN: 152220 Hom.: 629 Cov.: 32 AF XY: 0.0815 AC XY: 6062 AN XY: 74422

African (AFR) AF: 0.0388 AC: 1611 AN: 41550

American (AMR) AF: 0.0963 AC: 1473 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4822

European-Finnish (FIN) AF: 0.0938 AC: 994 AN: 10600

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7651 AN: 67988

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.103 Hom.: 2830

Bravo AF: 0.0826

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.72
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2518224; hg19: chr6-101906652; COSMIC: COSV59770367;