chr6-101648448-T-C

Variant names:

• chr6-101648448-T-C
• rs1337420
• NM_021956.5:c.541+21811T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021956.5(GRIK2):​c.541+21811T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,138 control chromosomes in the GnomAD database, including 1,048 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1048 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.541+21811T>C		intron_variant	Intron 4 of 16	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.541+21811T>C		intron_variant	Intron 4 of 16	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16533 AN: 152020 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.0802

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16552 AN: 152138 Hom.: 1048 Cov.: 32 AF XY: 0.113 AC XY: 8417 AN XY: 74372

African (AFR) AF: 0.0430 AC: 1787 AN: 41542

American (AMR) AF: 0.159 AC: 2427 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.0859 AC: 444 AN: 5166

South Asian (SAS) AF: 0.0803 AC: 388 AN: 4832

European-Finnish (FIN) AF: 0.198 AC: 2099 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8583 AN: 67976

Other (OTH) AF: 0.112 AC: 236 AN: 2116

Alfa AF: 0.115 Hom.: 908

Bravo AF: 0.105

Asia WGS AF: 0.0670 AC: 232 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

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

LitVar

Other links and lift over

dbSNP: rs1337420; hg19: chr6-102096323;