Variant chr6-102055442-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_021956.5(GRIK2):c.2424G>T(p.Glu808Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E808E) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GRIK2
NM_021956.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545

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 Uncertain_significance. Variant got 0 ACMG points.

PM1

In a topological_domain Extracellular (size 162) in uniprot entity GRIK2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_021956.5

BP4

Computational evidence support a benign effect (MetaRNN=0.13243717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5 linkuse as main transcript	c.2424G>T	p.Glu808Asp	missense_variant	16/17	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.2424G>T	p.Glu808Asp	missense_variant	16/17	5	NM_021956.5	ENSP00000358130	P4	Q13002-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250928

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.00328

Hom.:

5479

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

T;.;.;T;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

T;T;T;T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

N;N;N;.;.;.

MutationTaster

Benign

0.75

D;D;D;D;D;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.62

N;N;N;.;.;.

REVEL

Benign

0.10

Sift

Benign

0.69

T;T;T;.;.;.

Sift4G

Benign

0.45

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;.;.

Vest4

0.34

MutPred

0.35

Loss of disorder (P = 0.1299);Loss of disorder (P = 0.1299);Loss of disorder (P = 0.1299);.;.;.;

MVP

0.61

MPC

0.93

ClinPred

0.14

GERP RS

0.88

Varity_R

0.088

gMVP

0.62

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over