rs186727716
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_021956.5(GRIK2):āc.1360T>Cā(p.Tyr454His) variant causes a missense change. The variant allele was found at a frequency of 0.0000473 in 1,605,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 32)
Exomes š: 0.000045 ( 0 hom. )
Consequence
GRIK2
NM_021956.5 missense
NM_021956.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 4.63
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 Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04298386).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIK2 | NM_021956.5 | c.1360T>C | p.Tyr454His | missense_variant | 11/17 | ENST00000369134.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIK2 | ENST00000369134.9 | c.1360T>C | p.Tyr454His | missense_variant | 11/17 | 5 | NM_021956.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152180Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000107 AC: 27AN: 251188Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135776
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GnomAD4 exome AF: 0.0000447 AC: 65AN: 1453632Hom.: 0 Cov.: 27 AF XY: 0.0000387 AC XY: 28AN XY: 723766
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 03, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.1360T>C (p.Y454H) alteration is located in exon 10 (coding exon 10) of the GRIK2 gene. This alteration results from a T to C substitution at nucleotide position 1360, causing the tyrosine (Y) at amino acid position 454 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.;.;.;N;D
REVEL
Uncertain
Sift
Benign
T;T;T;.;.;.;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
B;B;B;.;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at