17-66558219-A-G

Variant names:

• chr17-66558219-A-G
• rs1860984
• NM_002737.3:c.288+61936A>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.288+61936A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 152,324 control chromosomes in the GnomAD database, including 881 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 0.094 (881 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• 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]

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 = 0.166 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.288+61936A>G		intron	N/A	NP_002728.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.288+61936A>G		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.288+61936A>G		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000284384.6	TSL:5	n.340+3640A>G		intron	N/A	ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14329 AN: 152206 Hom.: 881 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0941 AC: 14335 AN: 152324 Hom.: 881 Cov.: 33 AF XY: 0.0933 AC XY: 6948 AN XY: 74492

African (AFR) AF: 0.170 AC: 7055 AN: 41564

American (AMR) AF: 0.0782 AC: 1197 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3472

East Asian (EAS) AF: 0.0992 AC: 514 AN: 5180

South Asian (SAS) AF: 0.0664 AC: 321 AN: 4832

European-Finnish (FIN) AF: 0.0607 AC: 645 AN: 10626

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4218 AN: 68026

Other (OTH) AF: 0.0775 AC: 164 AN: 2116

Alfa AF: 0.0692 Hom.: 229

Bravo AF: 0.0990

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.051
DANN	Benign	0.37
PhyloP100		-1.9
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: rs1860984; hg19: chr17-64554337;