rs9322604

Variant names:

• chr6-101730857-G-A
• rs9322604
• NM_021956.5:c.951+44504G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-101730857-G-A
• chr6-101730857-G-T

Variant summary

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

The NM_021956.5(GRIK2):​c.951+44504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,532 control chromosomes in the GnomAD database, including 6,431 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 0.27 (6431 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.951+44504G>A		intron_variant	Intron 7 of 16	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.951+44504G>A		intron_variant	Intron 7 of 16	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40103 AN: 151414 Hom.: 6408 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.265 AC: 40175 AN: 151532 Hom.: 6431 Cov.: 32 AF XY: 0.270 AC XY: 19974 AN XY: 74032

African (AFR) AF: 0.419 AC: 17321 AN: 41374

American (AMR) AF: 0.270 AC: 4107 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2271 AN: 5126

South Asian (SAS) AF: 0.317 AC: 1526 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2658 AN: 10490

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.159 AC: 10750 AN: 67766

Other (OTH) AF: 0.245 AC: 513 AN: 2098

Alfa AF: 0.213 Hom.: 7936

Bravo AF: 0.273

Asia WGS AF: 0.393 AC: 1361 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.50
DANN	Benign	0.63
PhyloP100		-1.6
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: rs9322604; hg19: chr6-102178732;