rs2230494

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006254.4(PRKCD):c.1119G>A(p.Glu373Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,704 control chromosomes in the GnomAD database, including 60,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6478 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53992 hom. )

Consequence

PRKCD
NM_006254.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.23

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autoimmune lymphoproliferative syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal systemic lupus erythematosus type 16
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRKCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-53186199-G-A is Benign according to our data. Variant chr3-53186199-G-A is described in ClinVar as [Benign]. Clinvar id is 403345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCD	NM_006254.4 link	c.1119G>A	p.Glu373Glu	synonymous_variant	Exon 13 of 19	ENST00000330452.8	NP_006245.2	Q05655-1A0A024R328

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8 link	c.1119G>A	p.Glu373Glu	synonymous_variant	Exon 13 of 19	1	NM_006254.4	ENSP00000331602.3		Q05655-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43862

AN:

151990

Hom.:

6470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.298

GnomAD2 exomes

AF:

0.271

AC:

67887

AN:

250708

AF XY:

0.271

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.270

AC:

394688

AN:

1461596

Hom.:

53992

Cov.:

AF XY:

0.271

AC XY:

196889

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.329

AC:

11023

AN:

33476

American (AMR)

AF:

0.266

AC:

11861

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6590

AN:

26136

East Asian (EAS)

AF:

0.163

AC:

6481

AN:

39694

South Asian (SAS)

AF:

0.254

AC:

21929

AN:

86252

European-Finnish (FIN)

AF:

0.282

AC:

15067

AN:

53404

Middle Eastern (MID)

AF:

0.319

AC:

1839

AN:

5768

European-Non Finnish (NFE)

AF:

0.273

AC:

303481

AN:

1111844

Other (OTH)

AF:

0.272

AC:

16417

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

17643

35286

52929

70572

88215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10090

20180

30270

40360

50450

<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:

0.289

AC:

43906

AN:

152108

Hom.:

6478

Cov.:

AF XY:

0.287

AC XY:

21371

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.326

AC:

13515

AN:

41476

American (AMR)

AF:

0.292

AC:

4471

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

917

AN:

3470

East Asian (EAS)

AF:

0.209

AC:

1081

AN:

5172

South Asian (SAS)

AF:

0.256

AC:

1235

AN:

4828

European-Finnish (FIN)

AF:

0.282

AC:

2986

AN:

10590

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18765

AN:

67970

Other (OTH)

AF:

0.296

AC:

625

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1603

3206

4809

6412

8015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.278

Hom.:

6048

Bravo

AF:

0.290

Asia WGS

AF:

0.229

AC:

796

AN:

3478

EpiCase

AF:

0.288

EpiControl

AF:

0.290

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.4

(source)

DANN

Benign

0.54

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over