4-81193349-C-T

Variant names:

• chr4-81193349-C-T
• rs3733553
• NM_006259.3:c.461+11238G>A

Variant summary

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

The NM_006259.3(PRKG2):​c.461+11238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,038 control chromosomes in the GnomAD database, including 18,430 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 0.42 (18430 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 3 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-AS1 (HGNC:40478): (PRKG2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG2	NM_006259.3	MANE Select	c.461+11238G>A		intron	N/A	NP_006250.1	Q13237-1
	PRKG2	NM_001363401.2		c.461+11238G>A		intron	N/A	NP_001350330.1	A0A140VJM3
	PRKG2	NM_001282485.2		c.461+11238G>A		intron	N/A	NP_001269414.1	Q13237-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG2	ENST00000264399.6	TSL:5 MANE Select	c.461+11238G>A		intron	N/A	ENSP00000264399.1	Q13237-1
	PRKG2	ENST00000945150.1		c.461+11238G>A		intron	N/A	ENSP00000615209.1
	PRKG2	ENST00000853043.1		c.560+6666G>A		intron	N/A	ENSP00000523102.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63041 AN: 151916 Hom.: 18385 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.415 AC: 63139 AN: 152034 Hom.: 18430 Cov.: 32 AF XY: 0.408 AC XY: 30349 AN XY: 74328

African (AFR) AF: 0.820 AC: 34024 AN: 41482

American (AMR) AF: 0.331 AC: 5062 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2362 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1872 AN: 4812

European-Finnish (FIN) AF: 0.127 AC: 1344 AN: 10550

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15831 AN: 67966

Other (OTH) AF: 0.409 AC: 863 AN: 2108

Alfa AF: 0.304 Hom.: 28125

Bravo AF: 0.451

Asia WGS AF: 0.439 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs3733553; hg19: chr4-82114503;