Variant chr19-46675115-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016457.5(PRKD2):c.2342T>C(p.Ile781Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PRKD2
NM_016457.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

Variant links:

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]

PRKD2 links:

DACT3-AS1 (HGNC:44120): (DACT3 antisense RNA 1)

DACT3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33498412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD2	NM_016457.5 link	c.2342T>C	p.Ile781Thr	missense_variant	17/18	ENST00000291281.9	NP_057541.2	Q9BZL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9 link	c.2342T>C	p.Ile781Thr	missense_variant	17/18	1	NM_016457.5	ENSP00000291281.3		Q9BZL6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456806

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.2342T>C (p.I781T) alteration is located in exon 17 (coding exon 17) of the PRKD2 gene. This alteration results from a T to C substitution at nucleotide position 2342, causing the isoleucine (I) at amino acid position 781 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.0090

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

.;T;T;.;.

Eigen

Benign

0.081

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.95

.;.;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.31

T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.1

.;L;L;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.1

.;D;D;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.023

.;D;D;.;.

Sift4G

Benign

0.064

T;T;T;T;T

Polyphen

0.46

.;P;P;.;.

Vest4

0.36

MutPred

0.59

.;Loss of stability (P = 0.0189);Loss of stability (P = 0.0189);.;.;

MVP

0.31

MPC

1.7

ClinPred

0.98

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over