Variant 11-67282821-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001619.5(GRK2):c.1227+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,606,630 control chromosomes in the GnomAD database, including 641,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 45131 hom., cov: 33)

Exomes 𝑓: 0.90 ( 595897 hom. )

Consequence

GRK2
NM_001619.5 splice_region, intron

Scores

Splicing: ADA: 0.00006330

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

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:

GRK2 (HGNC:):

GRK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GRK2	NM_001619.5 linkuse as main transcript	c.1227+3G>A	splice_region_variant, intron_variant	ENST00000308595.10	NP_001610.2	P25098A0A0S2Z392
GRK2	XM_011544773.2 linkuse as main transcript	c.1137+3G>A	splice_region_variant, intron_variant		XP_011543075.1
GRK2	XR_007062455.1 linkuse as main transcript	n.1454+3G>A	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10 linkuse as main transcript	c.1227+3G>A		splice_region_variant, intron_variant		1	NM_001619.5	ENSP00000312262.5		P25098

Frequencies

GnomAD3 genomes

AF:

0.722

AC:

109715

AN:

152052

Hom.:

45133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.919

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.929

Gnomad FIN

AF:

0.867

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.773

GnomAD3 exomes

AF:

0.813

AC:

198129

AN:

243642

Hom.:

85291

AF XY:

0.841

AC XY:

111434

AN XY:

132482

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.540

Gnomad ASJ exome

AF:

0.919

Gnomad EAS exome

AF:

0.763

Gnomad SAS exome

AF:

0.929

Gnomad FIN exome

AF:

0.878

Gnomad NFE exome

AF:

0.925

Gnomad OTH exome

AF:

0.849

GnomAD4 exome

AF:

0.897

AC:

1304345

AN:

1454460

Hom.:

595897

Cov.:

AF XY:

0.902

AC XY:

652354

AN XY:

723602

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.916

Gnomad4 EAS exome

AF:

0.760

Gnomad4 SAS exome

AF:

0.929

Gnomad4 FIN exome

AF:

0.879

Gnomad4 NFE exome

AF:

0.933

Gnomad4 OTH exome

AF:

0.869

GnomAD4 genome

AF:

0.721

AC:

109728

AN:

152170

Hom.:

45131

Cov.:

AF XY:

0.723

AC XY:

53763

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.683

Gnomad4 ASJ

AF:

0.919

Gnomad4 EAS

AF:

0.764

Gnomad4 SAS

AF:

0.928

Gnomad4 FIN

AF:

0.867

Gnomad4 NFE

AF:

0.926

Gnomad4 OTH

AF:

0.774

Alfa

AF:

0.876

Hom.:

58567

Bravo

AF:

0.683

Asia WGS

AF:

0.772

AC:

2686

AN:

3478

EpiCase

AF:

0.929

EpiControl

AF:

0.929

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.056

SpliceAI score (max)

0.020

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