NM_021956.5:c.951+31825G>A

Variant names:

• chr6-101718178-G-A
• rs10485275
• NM_021956.5:c.951+31825G>A

Variant summary

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

The NM_021956.5(GRIK2):​c.951+31825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 151,714 control chromosomes in the GnomAD database, including 942 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 0.097 (942 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.951+31825G>A		intron_variant	Intron 7 of 16	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.951+31825G>A		intron_variant	Intron 7 of 16	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14722 AN: 151596 Hom.: 944 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0970 AC: 14716 AN: 151714 Hom.: 942 Cov.: 32 AF XY: 0.102 AC XY: 7538 AN XY: 74128

African (AFR) AF: 0.0655 AC: 2717 AN: 41492

American (AMR) AF: 0.106 AC: 1611 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 604 AN: 3460

East Asian (EAS) AF: 0.267 AC: 1364 AN: 5112

South Asian (SAS) AF: 0.251 AC: 1207 AN: 4812

European-Finnish (FIN) AF: 0.0739 AC: 780 AN: 10560

Middle Eastern (MID) AF: 0.203 AC: 59 AN: 290

European-Non Finnish (NFE) AF: 0.0890 AC: 6035 AN: 67802

Other (OTH) AF: 0.113 AC: 238 AN: 2098

Alfa AF: 0.0887 Hom.: 1190

Bravo AF: 0.0947

Asia WGS AF: 0.244 AC: 842 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10485275; hg19: chr6-102166053;