Variant 4-81171813-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006259.3(PRKG2):c.629-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,569,840 control chromosomes in the GnomAD database, including 55,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 12563 hom., cov: 32)

Exomes 𝑓: 0.22 ( 43395 hom. )

Consequence

PRKG2
NM_006259.3 intron

Scores

Splicing: ADA: 0.002930

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.96

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 links:

PRKG2-AS1 (HGNC:):

PRKG2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-81171813-C-T is Benign according to our data. Variant chr4-81171813-C-T is described in ClinVar as [Benign]. Clinvar id is 3060693.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG2	NM_006259.3 linkuse as main transcript	c.629-9G>A		intron_variant		ENST00000264399.6	NP_006250.1	Q13237-1A0A140VJM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6 linkuse as main transcript	c.629-9G>A		intron_variant		5	NM_006259.3	ENSP00000264399.1		Q13237-1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52215

AN:

151698

Hom.:

12534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.283

AC:

64362

AN:

227142

Hom.:

12115

AF XY:

0.281

AC XY:

34577

AN XY:

123016

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.369

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.221

AC:

313110

AN:

1418026

Hom.:

43395

Cov.:

AF XY:

0.225

AC XY:

158661

AN XY:

705872

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.365

Gnomad4 EAS exome

AF:

0.514

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.344

AC:

52297

AN:

151814

Hom.:

12563

Cov.:

AF XY:

0.342

AC XY:

25335

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.658

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.221

Hom.:

8389

Bravo

AF:

0.375

Asia WGS

AF:

0.453

AC:

1576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRKG2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.55

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0029

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over