17-66413218-A-G

Variant names:

• chr17-66413218-A-G
• rs11652956
• NM_002737.3:c.206-82983A>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.206-82983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,184 control chromosomes in the GnomAD database, including 1,529 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 0.12 (1529 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 6 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]

PRKCA-AS1 (HGNC:51347): (PRKCA antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002737.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.206-82983A>G		intron	N/A	NP_002728.2
	PRKCA-AS1	NR_110822.1		n.1129-456T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.206-82983A>G		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.206-82983A>G		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000284384.6	TSL:5	n.197-82983A>G		intron	N/A	ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18931 AN: 152064 Hom.: 1527 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.124 AC: 18932 AN: 152184 Hom.: 1529 Cov.: 32 AF XY: 0.132 AC XY: 9801 AN XY: 74390

African (AFR) AF: 0.0414 AC: 1718 AN: 41528

American (AMR) AF: 0.216 AC: 3298 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3468

East Asian (EAS) AF: 0.284 AC: 1470 AN: 5176

South Asian (SAS) AF: 0.207 AC: 995 AN: 4816

European-Finnish (FIN) AF: 0.160 AC: 1697 AN: 10594

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8630 AN: 68014

Other (OTH) AF: 0.150 AC: 317 AN: 2108

Alfa AF: 0.129 Hom.: 2224

Bravo AF: 0.123

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-0.024
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: rs11652956; hg19: chr17-64409336;