Variant rs2243355 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021956.5(GRIK2):c.2085+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,355,590 control chromosomes in the GnomAD database, including 67,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 5760 hom., cov: 32)

Exomes 𝑓: 0.31 ( 61693 hom. )

Consequence

GRIK2
NM_021956.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0920

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-101928642-G-A is Benign according to our data. Variant chr6-101928642-G-A is described in ClinVar as [Benign]. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 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.2085+10G>A		intron_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9 linkuse as main transcript	c.2085+10G>A		intron_variant		5	NM_021956.5	P4	Q13002-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36773

AN:

151938

Hom.:

5763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0572

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.0568

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.277

AC:

68711

AN:

248150

Hom.:

10733

AF XY:

0.284

AC XY:

38037

AN XY:

134034

show subpopulations

Gnomad AFR exome

AF:

0.0515

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.0602

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.313

AC:

377219

AN:

1203534

Hom.:

61693

Cov.:

AF XY:

0.314

AC XY:

191518

AN XY:

610474

show subpopulations

Gnomad4 AFR exome

AF:

0.0536

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.0553

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.242

AC:

36755

AN:

152056

Hom.:

5760

Cov.:

AF XY:

0.243

AC XY:

18051

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0570

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.0573

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.282

Hom.:

1762

Bravo

AF:

0.224

Asia WGS

AF:

0.132

AC:

459

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

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

Apr 07, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.1

DANN

Benign

0.64

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