rs2078153

Positions:

• chr17-66555697-C-G
• chr17-66555697-C-T

Variant summary

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

The NM_002737.3(PRKCA):​c.288+59414C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,890 control chromosomes in the GnomAD database, including 4,432 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 0.24 (4432 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

Genes affected

PRKCA (HGNC:9393): (protein kinase C alpha) 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 reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+59414C>G		intron_variant		ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.288+59414C>G		intron_variant		1	NM_002737.3	ENSP00000408695	P1
PRKCA	ENST00000578063.5	c.288+59414C>G		intron_variant, NMD_transcript_variant		1		ENSP00000462087
PRKCA	ENST00000284384.6	c.341+1118C>G		intron_variant, NMD_transcript_variant		5		ENSP00000284384

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36307 AN: 151772 Hom.: 4423 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.239 AC: 36342 AN: 151890 Hom.: 4432 Cov.: 31 AF XY: 0.239 AC XY: 17761 AN XY: 74248

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.259

Alfa AF: 0.232 Hom.: 520

Bravo AF: 0.238

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.71

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: rs2078153; hg19: chr17-64551815;