rs376836256
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_021956.5(GRIK2):c.1266G>A(p.Ala422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,611,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
GRIK2
NM_021956.5 synonymous
NM_021956.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.196
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 6-101818432-G-A is Benign according to our data. Variant chr6-101818432-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.196 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIK2 | NM_021956.5 | c.1266G>A | p.Ala422= | synonymous_variant | 10/17 | ENST00000369134.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIK2 | ENST00000369134.9 | c.1266G>A | p.Ala422= | synonymous_variant | 10/17 | 5 | NM_021956.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152172Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
15
AN:
152172
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250806Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135582
GnomAD3 exomes
AF:
AC:
33
AN:
250806
Hom.:
AF XY:
AC XY:
18
AN XY:
135582
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000101 AC: 147AN: 1459532Hom.: 1 Cov.: 28 AF XY: 0.000113 AC XY: 82AN XY: 726224
GnomAD4 exome
AF:
AC:
147
AN:
1459532
Hom.:
Cov.:
28
AF XY:
AC XY:
82
AN XY:
726224
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74460
GnomAD4 genome
?
AF:
AC:
15
AN:
152290
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
74460
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 25, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | GRIK2: BP4, BP7 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at