6-101226414-C-T

Variant names:

• chr6-101226414-C-T
• rs2797369
• ENST00000421544.6:c.-320-18216C>T

Variant summary

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

The ENST00000421544.6(GRIK2):​c.-320-18216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,066 control chromosomes in the GnomAD database, including 44,637 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 0.76 (44637 hom., cov: 32)
• Consequence: GRIK2 ENST00000421544.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107984041	XR_002956381.2	n.534-5256C>T		intron_variant	Intron 6 of 6
LOC107984041	XR_007059692.1	n.534-18216C>T		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000421544.6	c.-320-18216C>T		intron_variant	Intron 2 of 18	1		ENSP00000397026.1
GRIK2	ENST00000682090.1	c.-320-18216C>T		intron_variant	Intron 2 of 18			ENSP00000508130.1
GRIK2	ENST00000683774.1	n.206-18216C>T		intron_variant	Intron 3 of 16

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115896 AN: 151948 Hom.: 44606 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.763 AC: 115983 AN: 152066 Hom.: 44637 Cov.: 32 AF XY: 0.764 AC XY: 56814 AN XY: 74320

African (AFR) AF: 0.659 AC: 27334 AN: 41456

American (AMR) AF: 0.830 AC: 12680 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2724 AN: 3472

East Asian (EAS) AF: 0.673 AC: 3464 AN: 5146

South Asian (SAS) AF: 0.835 AC: 4012 AN: 4802

European-Finnish (FIN) AF: 0.786 AC: 8324 AN: 10596

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54770 AN: 67996

Other (OTH) AF: 0.801 AC: 1691 AN: 2110

Alfa AF: 0.788 Hom.: 29995

Bravo AF: 0.755

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.95
DANN	Benign	0.28
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs2797369; hg19: chr6-101674290;