NM_021956.5:c.2085+10G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 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=-0.87).

BP6

Variant 6-101928642-G-A is Benign according to our data. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar as Benign. Clinvar id is 129171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-101928642-G-A is described in CliVar 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 rank	MANE	Protein	UniProt
GRIK2	NM_021956.5 link	c.2085+10G>A		intron_variant	Intron 14 of 16	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.2085+10G>A		intron_variant	Intron 14 of 16	5	NM_021956.5	ENSP00000358130.6		Q13002-1F8WEZ8

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

GnomAD2 exomes

AF:

0.277

AC:

68711

AN:

248150

AF XY:

0.284

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 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

African (AFR)

AF:

0.0536

AC:

1521

AN:

28372

American (AMR)

AF:

0.237

AC:

10427

AN:

44004

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

8243

AN:

24444

East Asian (EAS)

AF:

0.0553

AC:

2121

AN:

38358

South Asian (SAS)

AF:

0.271

AC:

21902

AN:

80782

European-Finnish (FIN)

AF:

0.358

AC:

19023

AN:

53122

Middle Eastern (MID)

AF:

0.298

AC:

1562

AN:

5244

European-Non Finnish (NFE)

AF:

0.339

AC:

297132

AN:

877538

Other (OTH)

AF:

0.296

AC:

15288

AN:

51670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

12829

25658

38487

51316

64145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8408

16816

25224

33632

42040

<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:

0.242

AC:

36755

AN:

152056

Hom.:

5760

Cov.:

AF XY:

0.243

AC XY:

18051

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0570

AC:

2367

AN:

41510

American (AMR)

AF:

0.263

AC:

4006

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1086

AN:

3472

East Asian (EAS)

AF:

0.0573

AC:

296

AN:

5164

South Asian (SAS)

AF:

0.252

AC:

1217

AN:

4824

European-Finnish (FIN)

AF:

0.361

AC:

3811

AN:

10548

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23131

AN:

67956

Other (OTH)

AF:

0.251

AC:

532

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1292

2583

3875

5166

6458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.238

Hom.:

3697

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

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

Apr 07, 2022

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

-0.87

CADD

Benign

6.1

(source)

DANN

Benign

0.64

PhyloP100

-0.092

Mutation Taster

=100/0

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

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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