6-101530923-A-G

Variant names:

• chr6-101530923-A-G
• rs2518256
• NM_021956.5:c.116-91026A>G

Variant summary

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

The NM_021956.5(GRIK2):​c.116-91026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,008 control chromosomes in the GnomAD database, including 61,376 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 0.90 (61376 hom., cov: 31)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	NM_021956.5	MANE Select	c.116-91026A>G		intron	N/A	NP_068775.1
	GRIK2	NM_001166247.1		c.116-91026A>G		intron	N/A	NP_001159719.1
	GRIK2	NM_175768.3		c.116-91026A>G		intron	N/A	NP_786944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK2	ENST00000369134.9	TSL:5 MANE Select	c.116-91026A>G		intron	N/A	ENSP00000358130.6
	GRIK2	ENST00000421544.6	TSL:1	c.116-91026A>G		intron	N/A	ENSP00000397026.1
	GRIK2	ENST00000369138.5	TSL:1	c.116-91026A>G		intron	N/A	ENSP00000358134.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136298 AN: 151890 Hom.: 61327 Cov.: 31

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.897 AC: 136405 AN: 152008 Hom.: 61376 Cov.: 31 AF XY: 0.895 AC XY: 66487 AN XY: 74296

African (AFR) AF: 0.953 AC: 39573 AN: 41512

American (AMR) AF: 0.900 AC: 13701 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3006 AN: 3464

East Asian (EAS) AF: 0.930 AC: 4786 AN: 5146

South Asian (SAS) AF: 0.881 AC: 4254 AN: 4830

European-Finnish (FIN) AF: 0.820 AC: 8697 AN: 10602

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59481 AN: 67918

Other (OTH) AF: 0.897 AC: 1892 AN: 2110

Alfa AF: 0.892 Hom.: 21390

Bravo AF: 0.905

Asia WGS AF: 0.915 AC: 3182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.41
PhyloP100		-0.38
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: rs2518256; hg19: chr6-101978799;