2-45652443-G-C

Position:

• chr2-45652443-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005400.3(PRKCE):​c.343G>C​(p.Asp115His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRKCE NM_005400.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.13

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.343G>C	p.Asp115His	missense_variant	Exon 1 of 15	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.343G>C	p.Asp115His	missense_variant	Exon 1 of 15	1	NM_005400.3	ENSP00000306124.3
PRKCE	ENST00000421201.1	c.343G>C	p.Asp115His	missense_variant	Exon 2 of 3	4		ENSP00000394574.1
PRKCE	ENST00000462720.6	n.84G>C		non_coding_transcript_exon_variant	Exon 1 of 3	5
PRKCE	ENST00000480453.5	n.43G>C		non_coding_transcript_exon_variant	Exon 1 of 7	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.343G>C (p.D115H) alteration is located in exon 1 (coding exon 1) of the PRKCE gene. This alteration results from a G to C substitution at nucleotide position 343, causing the aspartic acid (D) at amino acid position 115 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.010	D;T
Sift4G	Benign	0.20	T;T
Polyphen		0.96	.;D
Vest4		0.72
MutPred		0.46		Gain of solvent accessibility (P = 0.0221);Gain of solvent accessibility (P = 0.0221);
MVP		0.87
MPC		2.0
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-45879582;