rs2227283

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_021956.5(GRIK2):c.2424G>A(p.Glu808=) 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.545

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 129175.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-102055442-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
GRIK2	NM_021956.5 linkuse as main transcript	c.2424G>A	p.Glu808=	synonymous_variant	16/17	ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9 linkuse as main transcript	c.2424G>A	p.Glu808=	synonymous_variant	16/17	5	NM_021956.5	P4	Q13002-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58166

AN:

151752

Hom.:

11495

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.398

AC:

99823

AN:

250928

Hom.:

20567

AF XY:

0.395

AC XY:

53607

AN XY:

135608

show subpopulations

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 SAS exome

AF:

0.286

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.:

AF XY:

0.416

AC XY:

302159

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.436

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.436

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.383

AC:

58179

AN:

151870

Hom.:

11493

Cov.:

AF XY:

0.380

AC XY:

28179

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.284

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.387

Hom.:

5479

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

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.8

DANN

Benign

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over