rs7741281

Variant names:

• chr6-101578136-G-A
• rs7741281
• NM_021956.5:c.116-43813G>A

Variant summary

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

The NM_021956.5(GRIK2):​c.116-43813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,186 control chromosomes in the GnomAD database, including 1,576 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 0.088 (1576 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.116-43813G>A		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.116-43813G>A		intron_variant	Intron 2 of 16	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13355 AN: 152068 Hom.: 1577 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.00707

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0613

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

GnomAD4 genome AF: 0.0879 AC: 13371 AN: 152186 Hom.: 1576 Cov.: 32 AF XY: 0.0843 AC XY: 6268 AN XY: 74386

African (AFR) AF: 0.270 AC: 11213 AN: 41518

American (AMR) AF: 0.0292 AC: 446 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5174

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4818

European-Finnish (FIN) AF: 0.00707 AC: 75 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0142 AC: 968 AN: 68000

Other (OTH) AF: 0.0607 AC: 128 AN: 2110

Alfa AF: 0.0314 Hom.: 534

Bravo AF: 0.0971

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.50
PhyloP100		-0.46
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: rs7741281; hg19: chr6-102026011;