2-45842155-C-T

Variant names:

• chr2-45842155-C-T
• rs4953268
• NM_005400.3:c.349-845C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005400.3(PRKCE):​c.349-845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,030 control chromosomes in the GnomAD database, including 44,717 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 0.77 (44717 hom., cov: 31)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.349-845C>T		intron_variant	Intron 1 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.349-845C>T		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116395 AN: 151912 Hom.: 44661 Cov.: 31

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.766 AC: 116509 AN: 152030 Hom.: 44717 Cov.: 31 AF XY: 0.764 AC XY: 56761 AN XY: 74306

African (AFR) AF: 0.769 AC: 31875 AN: 41446

American (AMR) AF: 0.822 AC: 12567 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2606 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3772 AN: 5174

South Asian (SAS) AF: 0.812 AC: 3909 AN: 4814

European-Finnish (FIN) AF: 0.664 AC: 7018 AN: 10562

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52121 AN: 67958

Other (OTH) AF: 0.763 AC: 1612 AN: 2112

Alfa AF: 0.769 Hom.: 22998

Bravo AF: 0.779

Asia WGS AF: 0.774 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.67
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4953268; hg19: chr2-46069294; COSMIC: COSV60327822;