19-46705224-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 85 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD2	NM_016457.5	MANE Select	c.512-575A>G		intron	N/A	NP_057541.2
	PRKD2	NM_001079880.2		c.512-575A>G		intron	N/A	NP_001073349.1	Q9BZL6-1
	PRKD2	NM_001079881.2		c.512-575A>G		intron	N/A	NP_001073350.1	Q9BZL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD2	ENST00000291281.9	TSL:1 MANE Select	c.512-575A>G		intron	N/A	ENSP00000291281.3	Q9BZL6-1
	PRKD2	ENST00000595515.5	TSL:2	c.512-575A>G		intron	N/A	ENSP00000470804.1	Q9BZL6-3
	PRKD2	ENST00000869062.1		c.512-575A>G		intron	N/A	ENSP00000539121.1

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

African (AFR) AF: 0.135 AC: 5544 AN: 41094

American (AMR) AF: 0.125 AC: 1891 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 435 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1026 AN: 5136

South Asian (SAS) AF: 0.143 AC: 689 AN: 4810

European-Finnish (FIN) AF: 0.190 AC: 1995 AN: 10486

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11137 AN: 67882

Other (OTH) AF: 0.130 AC: 274 AN: 2102

Alfa AF: 0.158 Hom.: 7162

Bravo AF: 0.149

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		-0.22
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: rs425105; hg19: chr19-47208481;