6-102055321-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021956.5(GRIK2):c.2312-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,593,100 control chromosomes in the GnomAD database, including 81,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 6700 hom., cov: 32)

Exomes 𝑓: 0.32 ( 74903 hom. )

Consequence

GRIK2
NM_021956.5 intron

Scores

Splicing: ADA: 0.00001126

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: -0.873

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-102055321-C-T is Benign according to our data. Variant chr6-102055321-C-T is described in ClinVar as [Benign]. Clinvar id is 129174.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-102055321-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5 link	c.2312-9C>T		intron_variant	Intron 15 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.2312-9C>T		intron_variant	Intron 15 of 16	5	NM_021956.5	ENSP00000358130.6		Q13002-1F8WEZ8

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44813

AN:

151738

Hom.:

6705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.306

AC:

75700

AN:

247068

Hom.:

11978

AF XY:

0.305

AC XY:

40726

AN XY:

133674

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.320

AC:

460650

AN:

1441246

Hom.:

74903

Cov.:

AF XY:

0.318

AC XY:

227928

AN XY:

717150

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.295

AC:

44814

AN:

151854

Hom.:

6700

Cov.:

AF XY:

0.295

AC XY:

21848

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.346

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.312

Hom.:

2452

Bravo

AF:

0.293

Asia WGS

AF:

0.272

AC:

947

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 28, 2020

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

-0.82

CADD

Benign

2.9

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.0

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