Variant rs2228418 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001619.5(GRK2):c.96C>A(p.Ile32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 1,337,718 control chromosomes in the GnomAD database, including 538,892 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 0.72 ( 44488 hom., cov: 29)

Exomes 𝑓: 0.91 ( 494404 hom. )

Consequence

GRK2
NM_001619.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

GRK2 (HGNC:289): (G protein-coupled receptor kinase 2) This gene encodes a member of the G protein-coupled receptor kinase family of proteins. The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. Data from rodent models supports a role for this gene in embryonic development, heart function and metabolism. Elevated expression of this gene has been observed in human patients with heart failure and Alzheimer's disease. [provided by RefSeq, Sep 2017]

GRK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP7

Synonymous conserved (PhyloP=1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK2	NM_001619.5 linkuse as main transcript	c.96C>A	p.Ile32=	synonymous_variant	1/21	ENST00000308595.10	NP_001610.2
GRK2	XR_007062455.1 linkuse as main transcript	n.323C>A		non_coding_transcript_exon_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10 linkuse as main transcript	c.96C>A	p.Ile32=	synonymous_variant	1/21	1	NM_001619.5	ENSP00000312262	P1
GRK2	ENST00000526285.1 linkuse as main transcript	c.96C>A	p.Ile32=	synonymous_variant	1/14	5		ENSP00000434126

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

108012

AN:

150366

Hom.:

44492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.917

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.929

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.868

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.770

GnomAD3 exomes

AF:

0.842

AC:

78711

AN:

93436

Hom.:

34574

AF XY:

0.867

AC XY:

46900

AN XY:

54104

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.917

Gnomad EAS exome

AF:

0.765

Gnomad SAS exome

AF:

0.929

Gnomad FIN exome

AF:

0.878

Gnomad NFE exome

AF:

0.926

Gnomad OTH exome

AF:

0.841

GnomAD4 exome

AF:

0.905

AC:

1074911

AN:

1187244

Hom.:

494404

Cov.:

AF XY:

0.908

AC XY:

529495

AN XY:

582910

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.539

Gnomad4 ASJ exome

AF:

0.913

Gnomad4 EAS exome

AF:

0.768

Gnomad4 SAS exome

AF:

0.928

Gnomad4 FIN exome

AF:

0.878

Gnomad4 NFE exome

AF:

0.934

Gnomad4 OTH exome

AF:

0.871

GnomAD4 genome

AF:

0.718

AC:

108020

AN:

150474

Hom.:

44488

Cov.:

AF XY:

0.720

AC XY:

52917

AN XY:

73524

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.683

Gnomad4 ASJ

AF:

0.917

Gnomad4 EAS

AF:

0.767

Gnomad4 SAS

AF:

0.929

Gnomad4 FIN

AF:

0.866

Gnomad4 NFE

AF:

0.926

Gnomad4 OTH

AF:

0.771

Alfa

AF:

0.881

Hom.:

35937

Bravo

AF:

0.679

Asia WGS

AF:

0.763

AC:

2435

AN:

3188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over