rs180799513

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021956.5(GRIK2):c.2312-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,603,348 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 143 hom. )

Consequence

GRIK2
NM_021956.5 splice_region, intron

Scores

Splicing: ADA: 0.0002136

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.653

Publications

0 publications found

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 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

GRIK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 6-102055322-T-G is Benign according to our data. Variant chr6-102055322-T-G is described in ClinVar as Benign. ClinVar VariationId is 129173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0635 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIK2	NM_021956.5	MANE Select	c.2312-8T>G	splice_region intron	N/A	NP_068775.1	Q13002-1
GRIK2	NM_001166247.1		c.2312-8T>G	splice_region intron	N/A	NP_001159719.1	Q8IY40
GRIK2	NM_175768.3		c.2312-8T>G	splice_region intron	N/A	NP_786944.1	Q8IY40

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIK2	ENST00000369134.9	TSL:5 MANE Select	c.2312-8T>G	splice_region intron	N/A	ENSP00000358130.6	Q13002-1
GRIK2	ENST00000421544.6	TSL:1	c.2312-8T>G	splice_region intron	N/A	ENSP00000397026.1	Q13002-1
GRIK2	ENST00000369138.5	TSL:1	c.2312-8T>G	splice_region intron	N/A	ENSP00000358134.1	Q13002-5

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

759

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.0119

AC:

2967

AN:

248478

AF XY:

0.00992

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.0690

Gnomad ASJ exome

AF:

0.00235

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00154

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.00920

GnomAD4 exome

AF:

0.00462

AC:

6698

AN:

1451160

Hom.:

143

Cov.:

AF XY:

0.00440

AC XY:

3180

AN XY:

722142

show subpopulations

African (AFR)

AF:

0.000874

AC:

AN:

33192

American (AMR)

AF:

0.0655

AC:

2899

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

25856

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39584

South Asian (SAS)

AF:

0.00547

AC:

469

AN:

85710

European-Finnish (FIN)

AF:

0.00158

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00403

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00257

AC:

2838

AN:

1103568

Other (OTH)

AF:

0.00455

AC:

273

AN:

59986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

293

586

878

1171

1464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00500

AC:

761

AN:

152188

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

356

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41548

American (AMR)

AF:

0.0283

AC:

432

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00249

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00326

AC:

222

AN:

68028

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.00867

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00357

EpiControl

AF:

0.00316

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.4

(source)

DANN

Benign

0.62

PhyloP100

0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.070

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over