Variant chr19-46678631-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000291281.9(PRKD2):c.2103C>G(p.Ile701Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,456,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PRKD2
ENST00000291281.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD2	NM_016457.5 linkuse as main transcript	c.2103C>G	p.Ile701Met	missense_variant	16/18	ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9 linkuse as main transcript	c.2103C>G	p.Ile701Met	missense_variant	16/18	1	NM_016457.5	ENSP00000291281	P1	Q9BZL6-1
DACT3-AS1	ENST00000690000.1 linkuse as main transcript	n.2511G>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1456538

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724922

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:

0.0000180

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

Feb 03, 2022

The c.2103C>G (p.I701M) alteration is located in exon 16 (coding exon 16) of the PRKD2 gene. This alteration results from a C to G substitution at nucleotide position 2103, causing the isoleucine (I) at amino acid position 701 to be replaced by a methionine (M). 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

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;T;.;.

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

.;.;D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.73

D;D;D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.4

.;L;L;.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.8

.;D;D;.;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

.;D;D;.;.

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

1.0

.;D;D;.;.

Vest4

0.84

MutPred

0.39

.;Gain of disorder (P = 0.1067);Gain of disorder (P = 0.1067);.;Gain of disorder (P = 0.1067);

MVP

0.72

MPC

2.6

ClinPred

0.98

GERP RS

2.4

Varity_R

0.099

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over