Genetic Variant PRKG2:c.*1155C>A (chr4-81088553-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006259.3(PRKG2):c.*1155C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,902 control chromosomes in the GnomAD database, including 9,883 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 0.26 ( 9883 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

PRKG2
NM_006259.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

17 publications found

Variant links:

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

PRKG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG2	NM_006259.3 link	c.*1155C>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000264399.6	NP_006250.1	Q13237-1A0A140VJM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6 link	c.*1155C>A		3_prime_UTR_variant	Exon 19 of 19	5	NM_006259.3	ENSP00000264399.1		Q13237-1
PRKG2	ENST00000395578.3 link	c.*1155C>A		downstream_gene_variant		5		ENSP00000378945.1		Q13237-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39619

AN:

151778

Hom.:

9843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.261

AC:

39716

AN:

151898

Hom.:

9883

Cov.:

AF XY:

0.260

AC XY:

19318

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.643

AC:

26607

AN:

41368

American (AMR)

AF:

0.198

AC:

3016

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3466

East Asian (EAS)

AF:

0.394

AC:

2029

AN:

5150

South Asian (SAS)

AF:

0.264

AC:

1270

AN:

4812

European-Finnish (FIN)

AF:

0.0706

AC:

748

AN:

10592

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0742

AC:

5044

AN:

67936

Other (OTH)

AF:

0.239

AC:

504

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1011

2021

3032

4042

5053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.132

Hom.:

13990

Bravo

AF:

0.290

Asia WGS

AF:

0.324

AC:

1126

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.19

(source)

DANN

Benign

0.33

PhyloP100

-1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over