17-66504825-C-T

Variant names:

• chr17-66504825-C-T
• rs2244497
• NM_002737.3:c.288+8542C>T

Variant summary

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

The NM_002737.3(PRKCA):​c.288+8542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,980 control chromosomes in the GnomAD database, including 25,189 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 0.56 (25189 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+8542C>T		intron_variant	Intron 3 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.288+8542C>T		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.288+8542C>T		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.279+8542C>T		intron_variant	Intron 3 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85301 AN: 151862 Hom.: 25182 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.562 AC: 85339 AN: 151980 Hom.: 25189 Cov.: 31 AF XY: 0.564 AC XY: 41924 AN XY: 74306

African (AFR) AF: 0.360 AC: 14925 AN: 41414

American (AMR) AF: 0.644 AC: 9841 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2788 AN: 5154

South Asian (SAS) AF: 0.469 AC: 2261 AN: 4816

European-Finnish (FIN) AF: 0.679 AC: 7183 AN: 10582

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44102 AN: 67962

Other (OTH) AF: 0.607 AC: 1281 AN: 2110

Alfa AF: 0.524 Hom.: 2549

Bravo AF: 0.554

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.65
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2244497; hg19: chr17-64500943;