rs11155845

Variant names:

• chr6-101059469-G-A
• rs11155845
• ENST00000683774.1:n.52-71160G>A

Variant summary

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

The ENST00000683774.1(GRIK2):​n.52-71160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 152,222 control chromosomes in the GnomAD database, including 403 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 0.041 (403 hom., cov: 32)
• Consequence: GRIK2 ENST00000683774.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder with impaired language and ataxia and with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC107984041 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107984041	XR_002956381.2	n.313-71160G>A		intron_variant	Intron 3 of 6
LOC107984041	XR_007059692.1	n.313-71160G>A		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000683774.1	n.52-71160G>A		intron_variant	Intron 1 of 16

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6155 AN: 152104 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0405 AC: 6172 AN: 152222 Hom.: 403 Cov.: 32 AF XY: 0.0427 AC XY: 3180 AN XY: 74414

African (AFR) AF: 0.0647 AC: 2686 AN: 41526

American (AMR) AF: 0.0620 AC: 947 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1548 AN: 5172

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4826

European-Finnish (FIN) AF: 0.0222 AC: 235 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00647 AC: 440 AN: 68016

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0196 Hom.: 196

Bravo AF: 0.0499

Asia WGS AF: 0.155 AC: 536 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.80
PhyloP100		0.029

Splicing

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

Other links and lift over

dbSNP: rs11155845; hg19: chr6-101507345;