17-66417266-A-T

Variant names:

• chr17-66417266-A-T
• rs2319523
• NM_002737.3:c.206-78935A>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.206-78935A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,462 control chromosomes in the GnomAD database, including 22,598 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 0.52 (22598 hom., cov: 30)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.206-78935A>T		intron_variant	Intron 2 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.206-78935A>T		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.206-78935A>T		intron_variant	Intron 2 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.197-78935A>T		intron_variant	Intron 2 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78217 AN: 151344 Hom.: 22592 Cov.: 30

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.517 AC: 78235 AN: 151462 Hom.: 22598 Cov.: 30 AF XY: 0.514 AC XY: 38017 AN XY: 73978

African (AFR) AF: 0.253 AC: 10423 AN: 41222

American (AMR) AF: 0.487 AC: 7424 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2357 AN: 3462

East Asian (EAS) AF: 0.448 AC: 2290 AN: 5110

South Asian (SAS) AF: 0.582 AC: 2786 AN: 4788

European-Finnish (FIN) AF: 0.592 AC: 6192 AN: 10466

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 44996 AN: 67882

Other (OTH) AF: 0.546 AC: 1147 AN: 2100

Alfa AF: 0.570 Hom.: 3289

Bravo AF: 0.492

Asia WGS AF: 0.447 AC: 1556 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	0.67
DANN	Benign	0.59
PhyloP100		-0.34
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: rs2319523; hg19: chr17-64413384;