Variant 4-81110459-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006259.3(PRKG2):c.1929C>T(p.Leu643=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,612,760 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

PRKG2
NM_006259.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.268

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 4-81110459-G-A is Benign according to our data. Variant chr4-81110459-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050415.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.268 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG2	NM_006259.3 linkuse as main transcript	c.1929C>T	p.Leu643=	synonymous_variant	15/19	ENST00000264399.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG2	ENST00000264399.6 linkuse as main transcript	c.1929C>T	p.Leu643=	synonymous_variant	15/19	5	NM_006259.3	P1	Q13237-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00132

AC:

329

AN:

249706

Hom.:

AF XY:

0.00118

AC XY:

159

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00255

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.00168

AC:

2459

AN:

1460554

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1155

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.0000902

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00207

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152206

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.000990

EpiCase

AF:

0.00104

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PRKG2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely 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

-0.86

CADD

Benign

1.4

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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