6-102070108-T-C

Position:

• chr6-102070108-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000681975.1(GRIK2):​c.2707+1617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 152,178 control chromosomes in the GnomAD database, including 141 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 0.033 (141 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GRIK2 ENST00000681975.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0329 (5010/152178) while in subpopulation NFE AF= 0.0466 (3165/67984). AF 95% confidence interval is 0.0452. There are 141 homozygotes in gnomad4. There are 2569 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 141 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5			downstream_gene_variant		ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9			downstream_gene_variant		5	NM_021956.5	P4

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5010 AN: 152060 Hom.: 141 Cov.: 32

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00682

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0239

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0329 AC: 5010 AN: 152178 Hom.: 141 Cov.: 32 AF XY: 0.0345 AC XY: 2569 AN XY: 74388

Gnomad4 AFR AF: 0.00717

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0466

Gnomad4 OTH AF: 0.0237

Bravo AF: 0.0249

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28383484; hg19: chr6-102517983;