2-45977900-T-G

Position:

• chr2-45977900-T-G

Variant summary

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

The NM_005400.3(PRKCE):​c.573-1076T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,166 control chromosomes in the GnomAD database, including 3,510 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 0.18 (3510 hom., cov: 31)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCE	NM_005400.3	c.573-1076T>G		intron_variant		ENST00000306156.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCE	ENST00000306156.8	c.573-1076T>G		intron_variant		1	NM_005400.3	P1
PRKCE	ENST00000476675.5	n.475-1076T>G		intron_variant, non_coding_transcript_variant		4
PRKCE	ENST00000480453.5	n.445-1076T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27464 AN: 152048 Hom.: 3504 Cov.: 31

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.181 AC: 27473 AN: 152166 Hom.: 3510 Cov.: 31 AF XY: 0.187 AC XY: 13908 AN XY: 74396

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.172

Alfa AF: 0.178 Hom.: 4191

Bravo AF: 0.197

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.48

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: rs13396424; hg19: chr2-46205039;