chr6-101799798-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_021956.5(GRIK2):c.1095+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,608,086 control chromosomes in the GnomAD database, including 39,052 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.26 ( 6998 hom., cov: 32)

Exomes 𝑓: 0.18 ( 32054 hom. )

Consequence

GRIK2
NM_021956.5 splice_region, intron

Scores

Splicing: ADA: 0.0001427

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0140

Publications

8 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 -13 ACMG points.

BP4

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

BP6

Variant 6-101799798-T-C is Benign according to our data. Variant chr6-101799798-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 129169.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 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.1095+7T>C	splice_region intron	N/A	NP_068775.1	Q13002-1
GRIK2	NM_001166247.1		c.1095+7T>C	splice_region intron	N/A	NP_001159719.1	Q8IY40
GRIK2	NM_175768.3		c.1095+7T>C	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.1095+7T>C	splice_region intron	N/A	ENSP00000358130.6	Q13002-1
GRIK2	ENST00000421544.6	TSL:1	c.1095+7T>C	splice_region intron	N/A	ENSP00000397026.1	Q13002-1
GRIK2	ENST00000369138.5	TSL:1	c.1095+7T>C	splice_region intron	N/A	ENSP00000358134.1	Q13002-5

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39882

AN:

151744

Hom.:

6966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.686

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.234

GnomAD2 exomes

AF:

0.251

AC:

62874

AN:

250648

AF XY:

0.246

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.180

AC:

262387

AN:

1456222

Hom.:

32054

Cov.:

AF XY:

0.183

AC XY:

132995

AN XY:

724850

show subpopulations

African (AFR)

AF:

0.440

AC:

14655

AN:

33330

American (AMR)

AF:

0.252

AC:

11225

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

3854

AN:

26078

East Asian (EAS)

AF:

0.620

AC:

24587

AN:

39632

South Asian (SAS)

AF:

0.350

AC:

30127

AN:

86078

European-Finnish (FIN)

AF:

0.197

AC:

10513

AN:

53354

Middle Eastern (MID)

AF:

0.161

AC:

924

AN:

5756

European-Non Finnish (NFE)

AF:

0.139

AC:

154074

AN:

1107242

Other (OTH)

AF:

0.207

AC:

12428

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

9468

18936

28405

37873

47341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6062

12124

18186

24248

30310

<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:

0.263

AC:

39976

AN:

151864

Hom.:

6998

Cov.:

AF XY:

0.271

AC XY:

20082

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.432

AC:

17861

AN:

41378

American (AMR)

AF:

0.242

AC:

3686

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

496

AN:

3464

East Asian (EAS)

AF:

0.687

AC:

3515

AN:

5120

South Asian (SAS)

AF:

0.364

AC:

1756

AN:

4826

European-Finnish (FIN)

AF:

0.211

AC:

2235

AN:

10568

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9694

AN:

67964

Other (OTH)

AF:

0.243

AC:

512

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1344

2688

4032

5376

6720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.187

Hom.:

10768

Bravo

AF:

0.270

Asia WGS

AF:

0.514

AC:

1789

AN:

3478

EpiCase

AF:

0.134

EpiControl

AF:

0.132

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.8

(source)

DANN

Benign

0.63

PhyloP100

-0.014

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.034

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over