6-101621952-G-A

Variant names:

• chr6-101621952-G-A
• NM_021956.5:c.119G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021956.5(GRIK2):​c.119G>A​(p.Gly40Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRIK2 NM_021956.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.119G>A	p.Gly40Asp	missense_variant	Exon 3 of 17	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.119G>A	p.Gly40Asp	missense_variant	Exon 3 of 17	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;.;.;T;T;.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;.;.;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-4.1	D;D;D;D;N;.;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D;D;D;D;T;.;.
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;.;.;.
Vest4		0.99
MutPred		0.68		Gain of phosphorylation at Y44 (P = 0.2011);Gain of phosphorylation at Y44 (P = 0.2011);Gain of phosphorylation at Y44 (P = 0.2011);Gain of phosphorylation at Y44 (P = 0.2011);.;.;.;
MVP		0.86
MPC		1.2
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.82
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-102069827;