Variant 2-46001554-G-A 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_005400.3(PRKCE):c.966+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,597,262 control chromosomes in the GnomAD database, including 2 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 Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

PRKCE
NM_005400.3 splice_region, intron

Scores

Splicing: ADA: 0.00009121

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.319

Variant links:

Genes affected

PRKCE (HGNC:9401): (protein kinase C epsilon) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior. [provided by RefSeq, Jul 2008]

PRKCE 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=-0.81).

BP6

Variant 2-46001554-G-A is Benign according to our data. Variant chr2-46001554-G-A is described in ClinVar as [Benign]. Clinvar id is 2650869.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCE	NM_005400.3 linkuse as main transcript	c.966+8G>A		splice_region_variant, intron_variant		ENST00000306156.8	NP_005391.1	Q02156L7RTI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8 linkuse as main transcript	c.966+8G>A		splice_region_variant, intron_variant		1	NM_005400.3	ENSP00000306124.3		Q02156
PRKCE	ENST00000394874.1 linkuse as main transcript	c.135+8G>A		splice_region_variant, intron_variant		3		ENSP00000378341.1		E9PBI2

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

184

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00119

AC:

278

AN:

234480

Hom.:

AF XY:

0.00123

AC XY:

158

AN XY:

128226

show subpopulations

Gnomad AFR exome

AF:

0.000469

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00205

GnomAD4 exome

AF:

0.00181

AC:

2619

AN:

1444980

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1267

AN XY:

719170

show subpopulations

Gnomad4 AFR exome

AF:

0.000480

Gnomad4 AMR exome

AF:

0.00227

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000513

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.00121

AC:

184

AN:

152282

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00146

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

PRKCE: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.0

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0

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