Variant 6-101682535-ATT-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_021956.5(GRIK2):c.724-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 836,274 control chromosomes in the GnomAD database, including 7 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 31)

Exomes 𝑓: 0.022 ( 3 hom. )

Consequence

GRIK2
NM_021956.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.566

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:

GRIK2 (HGNC:):

GRIK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 6-101682535-AT-A is Benign according to our data. Variant chr6-101682535-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 211106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0217 (14943/687692) while in subpopulation AFR AF= 0.0343 (602/17526). AF 95% confidence interval is 0.0321. There are 3 homozygotes in gnomad4_exome. There are 7533 alleles in male gnomad4_exome subpopulation. Median coverage is 11. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5 linkuse as main transcript	c.724-7delT		splice_region_variant, intron_variant		ENST00000369134.9	NP_068775.1	Q13002-1Q8IY40A0A8D9PH75A8K0H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9 linkuse as main transcript	c.724-7delT		splice_region_variant, intron_variant		5	NM_021956.5	ENSP00000358130.6		Q13002-1F8WEZ8

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

764

AN:

148500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00621

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00196

Gnomad SAS

AF:

0.00276

Gnomad FIN

AF:

0.000413

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000255

Gnomad OTH

AF:

0.00740

GnomAD4 exome

AF:

0.0217

AC:

14943

AN:

687692

Hom.:

Cov.:

AF XY:

0.0211

AC XY:

7533

AN XY:

356344

show subpopulations

Gnomad4 AFR exome

AF:

0.0343

Gnomad4 AMR exome

AF:

0.0303

Gnomad4 ASJ exome

AF:

0.0206

Gnomad4 EAS exome

AF:

0.0233

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0211

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.00515

AC:

765

AN:

148582

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

376

AN XY:

72408

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00216

Gnomad4 SAS

AF:

0.00298

Gnomad4 FIN

AF:

0.000413

Gnomad4 NFE

AF:

0.000255

Gnomad4 OTH

AF:

0.00732

Alfa

AF:

0.0334

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 08, 2014

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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