chr6-101043549-G-A

Variant names:

• chr6-101043549-G-A
• rs2749135
• ENST00000683774.1:n.51+80798G>A

Variant summary

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

The ENST00000683774.1(GRIK2):​n.51+80798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,120 control chromosomes in the GnomAD database, including 35,840 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 0.68 (35840 hom., cov: 32)
• Consequence: GRIK2 ENST00000683774.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107984041	XR_002956381.2	n.312+80798G>A		intron_variant	Intron 3 of 6
LOC107984041	XR_007059692.1	n.312+80798G>A		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000683774.1	n.51+80798G>A		intron_variant	Intron 1 of 16

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103980 AN: 152002 Hom.: 35811 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.684 AC: 104063 AN: 152120 Hom.: 35840 Cov.: 32 AF XY: 0.679 AC XY: 50448 AN XY: 74346

African (AFR) AF: 0.642 AC: 26645 AN: 41486

American (AMR) AF: 0.694 AC: 10605 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2626 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3449 AN: 5174

South Asian (SAS) AF: 0.474 AC: 2283 AN: 4814

European-Finnish (FIN) AF: 0.701 AC: 7406 AN: 10570

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48728 AN: 67996

Other (OTH) AF: 0.690 AC: 1459 AN: 2114

Alfa AF: 0.689 Hom.: 16578

Bravo AF: 0.689

Asia WGS AF: 0.594 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.34
PhyloP100		-0.037

Splicing

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

Other links and lift over

dbSNP: rs2749135; hg19: chr6-101491425;