chr4-81148295-G-A

Variant names:

• chr4-81148295-G-A
• rs7688672
• NM_006259.3:c.1154+589C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

PRKG2 Gene-Disease associations (from GenCC):

• acromesomelic dysplasia 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006259.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG2	NM_006259.3	MANE Select	c.1154+589C>T		intron	N/A	NP_006250.1
	PRKG2	NM_001363401.2		c.1154+589C>T		intron	N/A	NP_001350330.1
	PRKG2	NM_001282485.2		c.1154+589C>T		intron	N/A	NP_001269414.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG2	ENST00000264399.6	TSL:5 MANE Select	c.1154+589C>T		intron	N/A	ENSP00000264399.1
	PRKG2	ENST00000395578.3	TSL:5	c.1154+589C>T		intron	N/A	ENSP00000378945.1
	PRKG2	ENST00000628926.1	TSL:2	c.1154+589C>T		intron	N/A	ENSP00000486129.1

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

African (AFR) AF: 0.808 AC: 33495 AN: 41448

American (AMR) AF: 0.302 AC: 4614 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3468

East Asian (EAS) AF: 0.548 AC: 2819 AN: 5142

South Asian (SAS) AF: 0.385 AC: 1849 AN: 4798

European-Finnish (FIN) AF: 0.101 AC: 1064 AN: 10564

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12238 AN: 67952

Other (OTH) AF: 0.379 AC: 799 AN: 2108

Alfa AF: 0.239 Hom.: 11792

Bravo AF: 0.420

Asia WGS AF: 0.458 AC: 1590 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.17
PhyloP100		1.2
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: rs7688672; hg19: chr4-82069449;