19-46702503-C-G

Position:

• chr19-46702503-C-G

Variant summary

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

The NM_016457.5(PRKD2):​c.890-1391G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,838 control chromosomes in the GnomAD database, including 27,245 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 0.59 (27245 hom., cov: 31)
• Consequence: PRKD2 NM_016457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

Genes affected

PRKD2 (HGNC:17293): (protein kinase D2) The protein encoded by this gene belongs to the protein kinase D (PKD) family of serine/threonine protein kinases. This kinase can be activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells. It can bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral membrane protein exit from TGN. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD2	NM_016457.5	c.890-1391G>C		intron_variant		ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9	c.890-1391G>C		intron_variant		1	NM_016457.5	ENSP00000291281	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90258 AN: 151718 Hom.: 27222 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.595 AC: 90341 AN: 151838 Hom.: 27245 Cov.: 31 AF XY: 0.598 AC XY: 44321 AN XY: 74170

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.616

Alfa AF: 0.578 Hom.: 3197

Bravo AF: 0.605

Asia WGS AF: 0.495 AC: 1722 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	1.2
DANN	Benign	0.66

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: rs10411262; hg19: chr19-47205760;