Variant rs180799513 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021956.5(GRIK2):c.2312-8T>G variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002136

Clinical Significance

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

Conservation

PhyloP100: 0.653

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 129173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-102055322-T-G is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5 linkuse as main transcript	c.2312-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9 linkuse as main transcript	c.2312-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_021956.5	ENSP00000358130	P4	Q13002-1

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

GnomAD3 exomes

AF:

0.0119

AC:

2967

AN:

248478

Hom.:

104

AF XY:

0.00992

AC XY:

1333

AN XY:

134364

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 SAS exome

AF:

0.00505

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

Gnomad4 AFR exome

AF:

0.000874

Gnomad4 AMR exome

AF:

0.0655

Gnomad4 ASJ exome

AF:

0.00317

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00547

Gnomad4 FIN exome

AF:

0.00158

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.00455

GnomAD4 genome

AF:

0.00500

AC:

761

AN:

152188

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

356

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00326

Gnomad4 OTH

AF:

0.00474

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 24, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.4

DANN

Benign

0.62

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

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