17-66691328-A-G

Variant names:

• chr17-66691328-A-G
• rs1010544
• NM_002737.3:c.918+2281A>G

Variant summary

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

The NM_002737.3(PRKCA):​c.918+2281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,046 control chromosomes in the GnomAD database, including 9,571 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 0.33 (9571 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.918+2281A>G		intron_variant	Intron 8 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.918+2281A>G		intron_variant	Intron 8 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.918+2281A>G		intron_variant	Intron 8 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.*520+2281A>G		intron_variant	Intron 9 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49585 AN: 151928 Hom.: 9535 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.327 AC: 49669 AN: 152046 Hom.: 9571 Cov.: 32 AF XY: 0.326 AC XY: 24253 AN XY: 74328

African (AFR) AF: 0.539 AC: 22332 AN: 41420

American (AMR) AF: 0.277 AC: 4241 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2278 AN: 5172

South Asian (SAS) AF: 0.228 AC: 1098 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2812 AN: 10578

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15228 AN: 67988

Other (OTH) AF: 0.292 AC: 616 AN: 2108

Alfa AF: 0.298 Hom.: 6754

Bravo AF: 0.339

Asia WGS AF: 0.325 AC: 1129 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.085
DANN	Benign	0.47
PhyloP100		-3.2
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: rs1010544; hg19: chr17-64687446;