Variant 19-46704397-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016457.5(PRKD2):c.667-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,613,770 control chromosomes in the GnomAD database, including 36,625 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2420 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34205 hom. )

Consequence

PRKD2
NM_016457.5 splice_region, intron

Scores

Splicing: ADA: 0.00003207

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.608

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-46704397-G-A is Benign according to our data. Variant chr19-46704397-G-A is described in ClinVar as [Benign]. Clinvar id is 1242551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD2	NM_016457.5 linkuse as main transcript	c.667-6C>T		splice_region_variant, intron_variant		ENST00000291281.9	NP_057541.2	Q9BZL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9 linkuse as main transcript	c.667-6C>T		splice_region_variant, intron_variant		1	NM_016457.5	ENSP00000291281.3		Q9BZL6-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24468

AN:

152080

Hom.:

2420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0658

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.173

AC:

43299

AN:

250810

Hom.:

4475

AF XY:

0.179

AC XY:

24209

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.0637

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.209

AC:

305914

AN:

1461572

Hom.:

34205

Cov.:

AF XY:

0.209

AC XY:

152133

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0615

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.161

AC:

24470

AN:

152198

Hom.:

2420

Cov.:

AF XY:

0.159

AC XY:

11829

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.215

Hom.:

6551

Bravo

AF:

0.153

Asia WGS

AF:

0.0620

AC:

217

AN:

3478

EpiCase

AF:

0.235

EpiControl

AF:

0.220

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.28

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.0040

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