6-101682535-ATT-ATTT

Position:

• chr6-101682535-ATT-ATTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_021956.5(GRIK2):​c.724-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 849,588 control chromosomes in the GnomAD database, including 721 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.053 (651 hom., cov: 31)
  • Exomes 𝑓: 0.032 (70 hom.)
• Consequence: GRIK2 NM_021956.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

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]

GRIK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.724-7dupT		splice_region_variant, intron_variant		ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.724-7dupT		splice_region_variant, intron_variant		5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 7873 AN: 148522 Hom.: 649 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00276

Gnomad FIN AF: 0.000413

Gnomad MID AF: 0.00974

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.0322 AC: 22537 AN: 700984 Hom.: 70 Cov.: 11 AF XY: 0.0300 AC XY: 10901 AN XY: 363106

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0391

GnomAD4 genome AF: 0.0531 AC: 7887 AN: 148604 Hom.: 651 Cov.: 31 AF XY: 0.0510 AC XY: 3691 AN XY: 72404

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00256

Gnomad4 FIN AF: 0.000413

Gnomad4 NFE AF: 0.000824

Gnomad4 OTH AF: 0.0331

Bravo AF: 0.0601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2243352; hg19: chr6-102130410;