NM_021956.5:c.1524+9977C>T

Variant names:

• chr6-101869470-C-T
• rs1556995
• NM_021956.5:c.1524+9977C>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.1524+9977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 149,036 control chromosomes in the GnomAD database, including 38,557 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 0.71 (38557 hom., cov: 31)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 5 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	NM_021956.5	MANE Select	c.1524+9977C>T		intron	N/A	NP_068775.1
	GRIK2	NM_001166247.1		c.1524+9977C>T		intron	N/A	NP_001159719.1
	GRIK2	NM_175768.3		c.1524+9977C>T		intron	N/A	NP_786944.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000369134.9	TSL:5 MANE Select	c.1524+9977C>T		intron	N/A	ENSP00000358130.6
	GRIK2	ENST00000421544.6	TSL:1	c.1524+9977C>T		intron	N/A	ENSP00000397026.1
	GRIK2	ENST00000369138.5	TSL:1	c.1524+9977C>T		intron	N/A	ENSP00000358134.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 105782 AN: 148928 Hom.: 38544 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.710 AC: 105831 AN: 149036 Hom.: 38557 Cov.: 31 AF XY: 0.715 AC XY: 52161 AN XY: 72934

African (AFR) AF: 0.509 AC: 19719 AN: 38720

American (AMR) AF: 0.793 AC: 12031 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2817 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4725 AN: 5148

South Asian (SAS) AF: 0.887 AC: 4277 AN: 4820

European-Finnish (FIN) AF: 0.761 AC: 8050 AN: 10572

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51914 AN: 67844

Other (OTH) AF: 0.737 AC: 1537 AN: 2086

Alfa AF: 0.703 Hom.: 4768

Bravo AF: 0.688

Asia WGS AF: 0.846 AC: 2935 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		-0.17
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: rs1556995; hg19: chr6-102317345; COSMIC: COSV59766536;