rs2228418

chr11-67266795-C-Achr11-67266795-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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]

ACMG classification

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	UniProt
GRK2	NM_001619.5	c.96C>A	p.Ile32=	synonymous_variant	1/21	ENST00000308595.10
GRK2	XR_007062455.1	n.323C>A		non_coding_transcript_exon_variant	1/17

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.718 AC: 108012 AN: 150366 Hom.: 44492 Cov.: 29

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

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.: 29 AF XY: 0.908 AC XY: 529495 AN XY: 582910

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.: 29 AF XY: 0.720 AC XY: 52917 AN XY: 73524

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	14
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

Other links and lift over

dbSNP: rs2228418; hg19: chr11-67034266; COSMIC: COSV57951096; COSMIC: COSV57951096;