rs2138004

Positions:

• chr17-66526631-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002737.3(PRKCA):​c.288+30348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,956 control chromosomes in the GnomAD database, including 8,128 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 0.28 (8128 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+30348G>A		intron_variant		ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.288+30348G>A		intron_variant		1	NM_002737.3	ENSP00000408695	P1
PRKCA	ENST00000578063.5	c.288+30348G>A		intron_variant, NMD_transcript_variant		1		ENSP00000462087
PRKCA	ENST00000284384.6	c.281-27888G>A		intron_variant, NMD_transcript_variant		5		ENSP00000284384

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42879 AN: 151838 Hom.: 8098 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.283 AC: 42964 AN: 151956 Hom.: 8128 Cov.: 32 AF XY: 0.282 AC XY: 20974 AN XY: 74272

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.277

Alfa AF: 0.188 Hom.: 1611

Bravo AF: 0.305

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.040
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2138004; hg19: chr17-64522749;