Variant rs2230493 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006254.4(PRKCD):c.180T>C(p.Asp60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,930 control chromosomes in the GnomAD database, including 21,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1364 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20035 hom. )

Consequence

PRKCD
NM_006254.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.426

Variant links:

Genes affected

PRKCD (HGNC:9399): (protein kinase C delta) The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome. [provided by RefSeq, Aug 2017]

PRKCD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-53179641-T-C is Benign according to our data. Variant chr3-53179641-T-C is described in ClinVar as [Benign]. Clinvar id is 403344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.426 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCD	NM_006254.4 linkuse as main transcript	c.180T>C	p.Asp60=	synonymous_variant	4/19	ENST00000330452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCD	ENST00000330452.8 linkuse as main transcript	c.180T>C	p.Asp60=	synonymous_variant	4/19	1	NM_006254.4	P1	Q05655-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18706

AN:

152136

Hom.:

1363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0633

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.0175

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.127

AC:

31911

AN:

250908

Hom.:

2401

AF XY:

0.133

AC XY:

18090

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.0605

Gnomad AMR exome

AF:

0.0687

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0179

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.160

AC:

233451

AN:

1461676

Hom.:

20035

Cov.:

AF XY:

0.160

AC XY:

116659

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.0720

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.123

AC:

18703

AN:

152254

Hom.:

1364

Cov.:

AF XY:

0.121

AC XY:

8985

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0631

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.0173

Gnomad4 SAS

AF:

0.153

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.152

Hom.:

1993

Bravo

AF:

0.117

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

EpiCase

AF:

0.165

EpiControl

AF:

0.166

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.27

DANN

Benign

0.35

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

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