Variant 4-81104365-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006259.3(PRKG2):c.2126+5A>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,517,840 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

PRKG2
NM_006259.3 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.00003832

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.940

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-81104365-T-C is Benign according to our data. Variant chr4-81104365-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1711591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG2	NM_006259.3 linkuse as main transcript	c.2126+5A>G		splice_donor_5th_base_variant, intron_variant		ENST00000264399.6	NP_006250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6 linkuse as main transcript	c.2126+5A>G		splice_donor_5th_base_variant, intron_variant		5	NM_006259.3	ENSP00000264399	P1	Q13237-1

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000662

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00148

AC:

305

AN:

206468

Hom.:

AF XY:

0.00150

AC XY:

170

AN XY:

113238

show subpopulations

Gnomad AFR exome

AF:

0.0000839

Gnomad AMR exome

AF:

0.00184

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000998

Gnomad FIN exome

AF:

0.00200

Gnomad NFE exome

AF:

0.00172

Gnomad OTH exome

AF:

0.00492

GnomAD4 exome

AF:

0.00114

AC:

1563

AN:

1365592

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

846

AN XY:

678902

show subpopulations

Gnomad4 AFR exome

AF:

0.000314

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.0000419

Gnomad4 EAS exome

AF:

0.0000293

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00115

AC:

175

AN:

152248

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000662

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00142

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

PRKG2: BP4, BS2 -

PRKG2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 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

-0.89

CADD

Benign

0.070

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.030

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

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