19-46705224-T-C

Variant names:

• chr19-46705224-T-C
• rs425105
• NM_016457.5:c.512-575A>G

Variant summary

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

The NM_016457.5(PRKD2):​c.512-575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,334 control chromosomes in the GnomAD database, including 1,826 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 0.15 (1826 hom., cov: 30)
• Consequence: PRKD2 NM_016457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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 (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD2	NM_016457.5	c.512-575A>G		intron_variant	Intron 3 of 17	ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9	c.512-575A>G		intron_variant	Intron 3 of 17	1	NM_016457.5	ENSP00000291281.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23166 AN: 151220 Hom.: 1823 Cov.: 30

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.153 AC: 23189 AN: 151334 Hom.: 1826 Cov.: 30 AF XY: 0.151 AC XY: 11189 AN XY: 73894

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.130

Alfa AF: 0.160 Hom.: 3444

Bravo AF: 0.149

Asia WGS AF: 0.184 AC: 640 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	3.2
DANN	Benign	0.80

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: rs425105; hg19: chr19-47208481;