rs3213608
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_021956.5(GRIK2):c.2296G>A(p.Val766Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,589,202 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 5 hom., cov: 31)
Exomes 𝑓: 0.0010 ( 22 hom. )
Consequence
GRIK2
NM_021956.5 missense
NM_021956.5 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 6.95
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 Benign. Variant got -18 ACMG points.
PM1
?
In a topological_domain Extracellular (size 162) in uniprot entity GRIK2_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_021956.5
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00972122).
BP6
?
Variant 6-102035551-G-A is Benign according to our data. Variant chr6-102035551-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00279 (423/151370) while in subpopulation AMR AF= 0.024 (363/15118). AF 95% confidence interval is 0.022. There are 5 homozygotes in gnomad4. There are 234 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIK2 | NM_021956.5 | c.2296G>A | p.Val766Ile | missense_variant | 15/17 | ENST00000369134.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIK2 | ENST00000369134.9 | c.2296G>A | p.Val766Ile | missense_variant | 15/17 | 5 | NM_021956.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00279 AC: 422AN: 151256Hom.: 5 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00342 AC: 853AN: 249648Hom.: 14 AF XY: 0.00281 AC XY: 379AN XY: 134962
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GnomAD4 exome AF: 0.00101 AC: 1446AN: 1437832Hom.: 22 Cov.: 26 AF XY: 0.000931 AC XY: 667AN XY: 716476
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GnomAD4 genome ? AF: 0.00279 AC: 423AN: 151370Hom.: 5 Cov.: 31 AF XY: 0.00316 AC XY: 234AN XY: 73938
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Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 30, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Intellectual disability, autosomal recessive 6;C5562006:Neurodevelopmental disorder with impaired language and ataxia and with or without seizures Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 25, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.;.;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;N;.
REVEL
Benign
Sift
Benign
T;T;T;.;D;.
Sift4G
Benign
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