rs6925691

Variant names:

• chr6-101642645-T-A
• rs6925691
• NM_021956.5:c.541+16008T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-101642645-T-A
• chr6-101642645-T-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.541+16008T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,506 control chromosomes in the GnomAD database, including 8,314 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 0.32 (8314 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 1 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: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• neurodevelopmental disorder with impaired language and ataxia and with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 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.541+16008T>A		intron	N/A	NP_068775.1	Q13002-1
	GRIK2	NM_001166247.1		c.541+16008T>A		intron	N/A	NP_001159719.1	Q8IY40
	GRIK2	NM_175768.3		c.541+16008T>A		intron	N/A	NP_786944.1	Q8IY40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000369134.9	TSL:5 MANE Select	c.541+16008T>A		intron	N/A	ENSP00000358130.6	Q13002-1
	GRIK2	ENST00000421544.6	TSL:1	c.541+16008T>A		intron	N/A	ENSP00000397026.1	Q13002-1
	GRIK2	ENST00000369138.5	TSL:1	c.541+16008T>A		intron	N/A	ENSP00000358134.1	Q13002-5

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49020 AN: 151388 Hom.: 8299 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.324 AC: 49076 AN: 151506 Hom.: 8314 Cov.: 32 AF XY: 0.330 AC XY: 24441 AN XY: 74034

African (AFR) AF: 0.418 AC: 17303 AN: 41412

American (AMR) AF: 0.352 AC: 5351 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3462

East Asian (EAS) AF: 0.378 AC: 1948 AN: 5160

South Asian (SAS) AF: 0.318 AC: 1531 AN: 4810

European-Finnish (FIN) AF: 0.322 AC: 3394 AN: 10540

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17609 AN: 67628

Other (OTH) AF: 0.310 AC: 651 AN: 2100

Alfa AF: 0.285 Hom.: 814

Bravo AF: 0.330

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.54
DANN	Benign	0.39
PhyloP100		-0.93
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: rs6925691; hg19: chr6-102090520; COSMIC: COSV59766197;