rs2227283
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1
The NM_021956.5(GRIK2):c.2424G>A(p.Glu808=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,612,412 control chromosomes in the GnomAD database, including 141,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.38 ( 11493 hom., cov: 32)
Exomes 𝑓: 0.42 ( 130207 hom. )
Consequence
GRIK2
NM_021956.5 synonymous
NM_021956.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.545
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 6-102055442-G-A is Benign according to our data. Variant chr6-102055442-G-A is described in ClinVar as [Benign]. Clinvar id is 129175.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-102055442-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.545 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIK2 | NM_021956.5 | c.2424G>A | p.Glu808= | synonymous_variant | 16/17 | ENST00000369134.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIK2 | ENST00000369134.9 | c.2424G>A | p.Glu808= | synonymous_variant | 16/17 | 5 | NM_021956.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.383 AC: 58166AN: 151752Hom.: 11495 Cov.: 32
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GnomAD3 exomes AF: 0.398 AC: 99823AN: 250928Hom.: 20567 AF XY: 0.395 AC XY: 53607AN XY: 135608
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GnomAD4 exome AF: 0.419 AC: 611926AN: 1460542Hom.: 130207 Cov.: 35 AF XY: 0.416 AC XY: 302159AN XY: 726642
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GnomAD4 genome ? AF: 0.383 AC: 58179AN: 151870Hom.: 11493 Cov.: 32 AF XY: 0.380 AC XY: 28179AN XY: 74192
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 13, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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