NM_001619.5:c.503+29G>C

Variant names:

• chr11-67279929-G-C
• rs3730310
• NM_001619.5:c.503+29G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001619.5(GRK2):​c.503+29G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,605,810 control chromosomes in the GnomAD database, including 3,605 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 0.087 (1941 hom., cov: 33)
  • Exomes 𝑓: 0.0085 (1664 hom.)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Jeune syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001619.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK2	NM_001619.5	MANE Select	c.503+29G>C		intron	N/A	NP_001610.2	P25098

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK2	ENST00000308595.10	TSL:1 MANE Select	c.503+29G>C		intron	N/A	ENSP00000312262.5	P25098
	GRK2	ENST00000936739.1		c.530+29G>C		intron	N/A	ENSP00000606798.1
	GRK2	ENST00000951317.1		c.503+29G>C		intron	N/A	ENSP00000621376.1

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13212 AN: 152146 Hom.: 1939 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0583

GnomAD2 exomes AF: 0.0219 AC: 5458 AN: 249132 AF XY: 0.0159

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000712

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00854 AC: 12415 AN: 1453546 Hom.: 1664 Cov.: 29 AF XY: 0.00728 AC XY: 5267 AN XY: 723584

African (AFR) AF: 0.303 AC: 10122 AN: 33356

American (AMR) AF: 0.0159 AC: 710 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39658

South Asian (SAS) AF: 0.000511 AC: 44 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52884

Middle Eastern (MID) AF: 0.00867 AC: 50 AN: 5764

European-Non Finnish (NFE) AF: 0.000379 AC: 419 AN: 1104858

Other (OTH) AF: 0.0178 AC: 1068 AN: 60120

GnomAD4 genome AF: 0.0869 AC: 13232 AN: 152264 Hom.: 1941 Cov.: 33 AF XY: 0.0830 AC XY: 6182 AN XY: 74460

African (AFR) AF: 0.301 AC: 12509 AN: 41504

American (AMR) AF: 0.0339 AC: 518 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68034

Other (OTH) AF: 0.0577 AC: 122 AN: 2114

Alfa AF: 0.0446 Hom.: 160

Bravo AF: 0.0972

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.042
DANN	Benign	0.24
PhyloP100		-2.0
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3730310; hg19: chr11-67047400;