Variant rs3213607 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021956.5(GRIK2):c.2226C>A(p.Ile742=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 1,608,300 control chromosomes in the GnomAD database, including 3,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.068 ( 351 hom., cov: 31)

Exomes 𝑓: 0.065 ( 3261 hom. )

Consequence

GRIK2
NM_021956.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.309

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-102035481-C-A is Benign according to our data. Variant chr6-102035481-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 129172.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK2	NM_021956.5 linkuse as main transcript	c.2226C>A	p.Ile742=	synonymous_variant	15/17	ENST00000369134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK2	ENST00000369134.9 linkuse as main transcript	c.2226C>A	p.Ile742=	synonymous_variant	15/17	5	NM_021956.5	P4	Q13002-1

Frequencies

GnomAD3 genomes

AF:

0.0684

AC:

10328

AN:

151102

Hom.:

350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0813

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.0480

Gnomad EAS

AF:

0.0541

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.0646

GnomAD3 exomes

AF:

0.0649

AC:

16261

AN:

250652

Hom.:

591

AF XY:

0.0642

AC XY:

8698

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.0385

Gnomad EAS exome

AF:

0.0499

Gnomad SAS exome

AF:

0.0584

Gnomad FIN exome

AF:

0.0717

Gnomad NFE exome

AF:

0.0644

Gnomad OTH exome

AF:

0.0616

GnomAD4 exome

AF:

0.0652

AC:

95072

AN:

1457080

Hom.:

3261

Cov.:

AF XY:

0.0650

AC XY:

47097

AN XY:

725072

show subpopulations

Gnomad4 AFR exome

AF:

0.0797

Gnomad4 AMR exome

AF:

0.0740

Gnomad4 ASJ exome

AF:

0.0414

Gnomad4 EAS exome

AF:

0.0649

Gnomad4 SAS exome

AF:

0.0576

Gnomad4 FIN exome

AF:

0.0744

Gnomad4 NFE exome

AF:

0.0656

Gnomad4 OTH exome

AF:

0.0609

GnomAD4 genome

AF:

0.0683

AC:

10334

AN:

151220

Hom.:

351

Cov.:

AF XY:

0.0685

AC XY:

5060

AN XY:

73852

show subpopulations

Gnomad4 AFR

AF:

0.0813

Gnomad4 AMR

AF:

0.0598

Gnomad4 ASJ

AF:

0.0480

Gnomad4 EAS

AF:

0.0540

Gnomad4 SAS

AF:

0.0552

Gnomad4 FIN

AF:

0.0767

Gnomad4 NFE

AF:

0.0651

Gnomad4 OTH

AF:

0.0668

Alfa

AF:

0.0601

Hom.:

345

Bravo

AF:

0.0662

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

EpiCase

AF:

0.0590

EpiControl

AF:

0.0614

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.4

DANN

Benign

0.68

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over