ENST00000681975.1:c.2708-1578T>C

Variant names:

• chr6-102078603-T-C
• rs2782900
• ENST00000681975.1:c.2708-1578T>C

Variant summary

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

The ENST00000681975.1(GRIK2):​c.2708-1578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,148 control chromosomes in the GnomAD database, including 5,218 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 0.25 (5218 hom., cov: 32)
• Consequence: GRIK2 ENST00000681975.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000681975.1	c.2708-1578T>C		intron_variant	Intron 17 of 17			ENSP00000508014.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38484 AN: 152030 Hom.: 5218 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.253 AC: 38484 AN: 152148 Hom.: 5218 Cov.: 32 AF XY: 0.250 AC XY: 18592 AN XY: 74372

African (AFR) AF: 0.167 AC: 6950 AN: 41508

American (AMR) AF: 0.244 AC: 3729 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3464

East Asian (EAS) AF: 0.0954 AC: 495 AN: 5186

South Asian (SAS) AF: 0.163 AC: 786 AN: 4830

European-Finnish (FIN) AF: 0.306 AC: 3238 AN: 10584

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21486 AN: 67980

Other (OTH) AF: 0.260 AC: 548 AN: 2108

Alfa AF: 0.293 Hom.: 25192

Bravo AF: 0.248

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs2782900; hg19: chr6-102526478;