rs2711285

Positions:

• chr2-46002710-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005400.3(PRKCE):​c.966+1164C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,008 control chromosomes in the GnomAD database, including 10,263 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10263 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.966+1164C>G		intron_variant		ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.966+1164C>G		intron_variant		1	NM_005400.3	ENSP00000306124	P1
PRKCE	ENST00000394874.1	c.135+1164C>G		intron_variant		3		ENSP00000378341

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55248 AN: 151890 Hom.: 10250 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.354

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55290 AN: 152008 Hom.: 10263 Cov.: 32 AF XY: 0.365 AC XY: 27158 AN XY: 74310

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.352

Alfa AF: 0.363 Hom.: 1245

Bravo AF: 0.373

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.93
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs2711285; hg19: chr2-46229849;