rs3213607

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021956.5(GRIK2):c.2226C>A(p.Ile742Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 1,608,300 control chromosomes in the GnomAD database, including 3,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.068 ( 351 hom., cov: 31)

Exomes 𝑓: 0.065 ( 3261 hom. )

Consequence

GRIK2
NM_021956.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.309

Publications

19 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: 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

GRIK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-102035481-C-A is Benign according to our data. Variant chr6-102035481-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 129172.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5 link	c.2226C>A	p.Ile742Ile	synonymous_variant	Exon 15 of 17	ENST00000369134.9	NP_068775.1	Q13002-1Q8IY40A0A8D9PH75A8K0H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9 link	c.2226C>A	p.Ile742Ile	synonymous_variant	Exon 15 of 17	5	NM_021956.5	ENSP00000358130.6		Q13002-1F8WEZ8

Frequencies

GnomAD3 genomes

AF:

0.0684

AC:

10328

AN:

151102

Hom.:

350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0813

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.0480

Gnomad EAS

AF:

0.0541

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.0646

GnomAD2 exomes

AF:

0.0649

AC:

16261

AN:

250652

AF XY:

0.0642

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.0385

Gnomad EAS exome

AF:

0.0499

Gnomad FIN exome

AF:

0.0717

Gnomad NFE exome

AF:

0.0644

Gnomad OTH exome

AF:

0.0616

GnomAD4 exome

AF:

0.0652

AC:

95072

AN:

1457080

Hom.:

3261

Cov.:

AF XY:

0.0650

AC XY:

47097

AN XY:

725072

show subpopulations

African (AFR)

AF:

0.0797

AC:

2647

AN:

33216

American (AMR)

AF:

0.0740

AC:

3297

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.0414

AC:

1076

AN:

25988

East Asian (EAS)

AF:

0.0649

AC:

2572

AN:

39642

South Asian (SAS)

AF:

0.0576

AC:

4959

AN:

86098

European-Finnish (FIN)

AF:

0.0744

AC:

3974

AN:

53390

Middle Eastern (MID)

AF:

0.0298

AC:

171

AN:

5738

European-Non Finnish (NFE)

AF:

0.0656

AC:

72715

AN:

1108302

Other (OTH)

AF:

0.0609

AC:

3661

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

4141

8282

12423

16564

20705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2774

5548

8322

11096

13870

<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:

0.0683

AC:

10334

AN:

151220

Hom.:

351

Cov.:

AF XY:

0.0685

AC XY:

5060

AN XY:

73852

show subpopulations

African (AFR)

AF:

0.0813

AC:

3363

AN:

41354

American (AMR)

AF:

0.0598

AC:

903

AN:

15094

Ashkenazi Jewish (ASJ)

AF:

0.0480

AC:

165

AN:

3436

East Asian (EAS)

AF:

0.0540

AC:

275

AN:

5094

South Asian (SAS)

AF:

0.0552

AC:

266

AN:

4816

European-Finnish (FIN)

AF:

0.0767

AC:

812

AN:

10582

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0651

AC:

4396

AN:

67542

Other (OTH)

AF:

0.0668

AC:

140

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

485

969

1454

1938

2423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0622

Hom.:

554

Bravo

AF:

0.0662

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

EpiCase

AF:

0.0590

EpiControl

AF:

0.0614

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.4

(source)

DANN

Benign

0.68

PhyloP100

-0.31

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over