rs2227283

Variant names:

• chr6-102055442-G-A
• rs2227283
• NM_021956.5:c.2424G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-102055442-G-A
• chr6-102055442-G-C
• chr6-102055442-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_021956.5(GRIK2):​c.2424G>A​(p.Glu808Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,612,412 control chromosomes in the GnomAD database, including 141,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11493 hom., cov: 32)
  • Exomes 𝑓: 0.42 (130207 hom.)
• Consequence: GRIK2 NM_021956.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:4
• Conservation: PhyloP100: 0.545
• Publications: 29 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 6-102055442-G-A is Benign according to our data. Variant chr6-102055442-G-A is described in ClinVar as Benign. ClinVar VariationId is 129175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.545 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.2424G>A	p.Glu808Glu	synonymous_variant	Exon 16 of 17	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.2424G>A	p.Glu808Glu	synonymous_variant	Exon 16 of 17	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58166 AN: 151752 Hom.: 11495 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.397

GnomAD2 exomes AF: 0.398 AC: 99823 AN: 250928 AF XY: 0.395

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.346

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.419 AC: 611926 AN: 1460542 Hom.: 130207 Cov.: 35 AF XY: 0.416 AC XY: 302159 AN XY: 726642

African (AFR) AF: 0.280 AC: 9364 AN: 33452

American (AMR) AF: 0.436 AC: 19479 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10832 AN: 26122

East Asian (EAS) AF: 0.344 AC: 13643 AN: 39676

South Asian (SAS) AF: 0.292 AC: 25162 AN: 86234

European-Finnish (FIN) AF: 0.414 AC: 22122 AN: 53410

Middle Eastern (MID) AF: 0.442 AC: 2547 AN: 5762

European-Non Finnish (NFE) AF: 0.436 AC: 484220 AN: 1110834

Other (OTH) AF: 0.407 AC: 24557 AN: 60338

GnomAD4 genome AF: 0.383 AC: 58179 AN: 151870 Hom.: 11493 Cov.: 32 AF XY: 0.380 AC XY: 28179 AN XY: 74192

African (AFR) AF: 0.284 AC: 11757 AN: 41458

American (AMR) AF: 0.414 AC: 6301 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3466

East Asian (EAS) AF: 0.347 AC: 1770 AN: 5108

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4812

European-Finnish (FIN) AF: 0.408 AC: 4303 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29693 AN: 67940

Other (OTH) AF: 0.393 AC: 827 AN: 2104

Alfa AF: 0.337 Hom.: 7591

Bravo AF: 0.383

Asia WGS AF: 0.294 AC: 1026 AN: 3478

EpiCase AF: 0.437

EpiControl AF: 0.442

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:3

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided Benign:1

Feb 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.8
DANN	Benign	0.52
PhyloP100		0.55
Mutation Taster		=99/1	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: rs2227283; hg19: chr6-102503317; COSMIC: COSV59720635;