2-45949823-C-A

Variant names:

• chr2-45949823-C-A
• rs6751349
• NM_005400.3:c.413-26606C>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.413-26606C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,440 control chromosomes in the GnomAD database, including 3,737 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 0.19 (3737 hom., cov: 31)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	NM_005400.3	MANE Select	c.413-26606C>A		intron	N/A	NP_005391.1	Q02156

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	ENST00000306156.8	TSL:1 MANE Select	c.413-26606C>A		intron	N/A	ENSP00000306124.3	Q02156
	PRKCE	ENST00000872579.1		c.413-51581C>A		intron	N/A	ENSP00000542638.1
	PRKCE	ENST00000476675.5	TSL:4	n.315-26606C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29217 AN: 151324 Hom.: 3718 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.193 AC: 29272 AN: 151440 Hom.: 3737 Cov.: 31 AF XY: 0.190 AC XY: 14049 AN XY: 73956

African (AFR) AF: 0.355 AC: 14676 AN: 41306

American (AMR) AF: 0.126 AC: 1923 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3468

East Asian (EAS) AF: 0.0237 AC: 122 AN: 5154

South Asian (SAS) AF: 0.236 AC: 1132 AN: 4800

European-Finnish (FIN) AF: 0.0863 AC: 892 AN: 10334

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9532 AN: 67872

Other (OTH) AF: 0.163 AC: 341 AN: 2094

Alfa AF: 0.153 Hom.: 3512

Bravo AF: 0.198

Asia WGS AF: 0.135 AC: 471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.53
PhyloP100		-0.21
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: rs6751349; hg19: chr2-46176962;