Genetic Variant GRIK2:c.1095+7T>C (chr6-101799798-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 129169.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-101799798-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5 link	c.1095+7T>C		splice_region_variant, intron_variant	Intron 8 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.1095+7T>C		splice_region_variant, intron_variant	Intron 8 of 16	5	NM_021956.5	ENSP00000358130.6		Q13002-1F8WEZ8

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

GnomAD3 exomes

AF:

0.251

AC:

62874

AN:

250648

Hom.:

10973

AF XY:

0.246

AC XY:

33341

AN XY:

135452

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 SAS exome

AF:

0.361

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

Gnomad4 AFR exome

AF:

0.440

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.620

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.263

AC:

39976

AN:

151864

Hom.:

6998

Cov.:

AF XY:

0.271

AC XY:

20082

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.432

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.687

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.170

Hom.:

5819

Bravo

AF:

0.270

Asia WGS

AF:

0.514

AC:

1789

AN:

3478

EpiCase

AF:

0.134

EpiControl

AF:

0.132

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

-0.87

CADD

Benign

4.8

DANN

Benign

0.63

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

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