2-45998826-G-A

Variant names:

• chr2-45998826-G-A
• rs2595218
• NM_005400.3:c.824-2578G>A

Variant summary

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

The NM_005400.3(PRKCE):​c.824-2578G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,918 control chromosomes in the GnomAD database, including 10,869 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 0.37 (10869 hom., cov: 33)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005400.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	NM_005400.3	MANE Select	c.824-2578G>A		intron	N/A	NP_005391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	ENST00000306156.8	TSL:1 MANE Select	c.824-2578G>A		intron	N/A	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56682 AN: 151800 Hom.: 10853 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.373 AC: 56734 AN: 151918 Hom.: 10869 Cov.: 33 AF XY: 0.377 AC XY: 27964 AN XY: 74244

African (AFR) AF: 0.347 AC: 14381 AN: 41436

American (AMR) AF: 0.479 AC: 7319 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1262 AN: 3458

East Asian (EAS) AF: 0.529 AC: 2738 AN: 5178

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4818

European-Finnish (FIN) AF: 0.358 AC: 3771 AN: 10536

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24553 AN: 67906

Other (OTH) AF: 0.360 AC: 758 AN: 2108

Alfa AF: 0.367 Hom.: 26944

Bravo AF: 0.385

Asia WGS AF: 0.368 AC: 1278 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-0.14
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: rs2595218; hg19: chr2-46225965;