chr19-46689692-G-C

Position:

• chr19-46689692-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016457.5(PRKD2):​c.1816C>G​(p.Arg606Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRKD2 NM_016457.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.85

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD2	NM_016457.5	c.1816C>G	p.Arg606Gly	missense_variant	14/18	ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9	c.1816C>G	p.Arg606Gly	missense_variant	14/18	1	NM_016457.5	ENSP00000291281.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

PRKD2-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 11, 2024

The PRKD2 c.1816C>G variant is predicted to result in the amino acid substitution p.Arg606Gly. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;T;T;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;.;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.0	.;L;L;.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	.;N;N;.;.
REVEL	Uncertain	0.55
Sift	Benign	0.62	.;T;T;.;.
Sift4G	Benign	0.47	T;T;T;T;T
Polyphen		0.46	.;P;P;.;.
Vest4		0.56
MutPred		0.47		.;Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);.;Loss of solvent accessibility (P = 0.0509);
MVP		0.81
MPC		2.2
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.33
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-47192949;