chr6-101889856-A-G

Variant summary

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

The NM_021956.5(GRIK2):ā€‹c.1741A>Gā€‹(p.Ile581Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,445,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

GRIK2
NM_021956.5 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIK2NM_021956.5 linkuse as main transcriptc.1741A>G p.Ile581Val missense_variant 12/17 ENST00000369134.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIK2ENST00000369134.9 linkuse as main transcriptc.1741A>G p.Ile581Val missense_variant 12/175 NM_021956.5 P4Q13002-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.0000111
AC:
16
AN:
1445944
Hom.:
0
Cov.:
28
AF XY:
0.0000125
AC XY:
9
AN XY:
720386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000137
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 22, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.;.;T;.;T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D;T
M_CAP
Uncertain
0.089
D
MetaRNN
Uncertain
0.60
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.70
D
MutationAssessor
Benign
0.12
N;N;N;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.65
N;N;N;.;.;.;N
REVEL
Uncertain
0.58
Sift
Benign
0.49
T;T;T;.;.;.;T
Sift4G
Benign
0.76
T;T;T;T;T;T;T
Polyphen
0.93
P;P;P;.;.;.;.
Vest4
0.49
MutPred
0.45
Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);.;.;.;.;
MVP
0.80
MPC
2.0
ClinPred
0.96
D
GERP RS
5.6
Varity_R
0.15
gMVP
0.38

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.

Other links and lift over

dbSNP: rs1554281005; hg19: chr6-102337731; API