rs7688672

chr4-81148295-G-Achr4-81148295-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006259.3(PRKG2):c.1154+589C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,938 control chromosomes in the GnomAD database, including 17,153 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 0.38 (17153 hom., cov: 32)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

PRKG2 (HGNC:9416): (protein kinase cGMP-dependent 2) This gene encodes a protein that belongs to the serine/threonine protein kinase family of proteins. The encoded protein binds to and inhibits the activation of several receptor tyrosine kinases. The membrane-bound protein is a regulator of intestinal secretion, bone growth and renin secretion. Alternate splicing results in multiple transcript variants encoding distinct isoforms whose regulatory N-termini differ in length but whose C-terminal catalytic domains are identical. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG2	NM_006259.3	c.1154+589C>T		intron_variant		ENST00000264399.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG2	ENST00000264399.6	c.1154+589C>T		intron_variant		5	NM_006259.3	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58206 AN: 151822 Hom.: 17110 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58304 AN: 151938 Hom.: 17153 Cov.: 32 AF XY: 0.380 AC XY: 28198 AN XY: 74272

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.379

Alfa AF: 0.225 Hom.: 7089

Bravo AF: 0.420

Asia WGS AF: 0.458 AC: 1590 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.9
Dann	Benign	0.17

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: rs7688672; hg19: chr4-82069449;