Variant chr14-29577320-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002742.3(PRKD1):c.2657A>G(p.Asn886Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,856 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 8 hom. )

Consequence

PRKD1
NM_002742.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.197

Variant links:

Genes affected

PRKD1 (HGNC:9407): (protein kinase D1) The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion. [provided by RefSeq, Jan 2017]

PRKD1 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 (MetaRNN=0.0019049346).

BP6

Variant 14-29577320-T-C is Benign according to our data. Variant chr14-29577320-T-C is described in ClinVar as [Benign]. Clinvar id is 784280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00578 (880/152252) while in subpopulation AFR AF= 0.0194 (806/41552). AF 95% confidence interval is 0.0183. There are 11 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 880 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKD1	NM_002742.3 linkuse as main transcript	c.2657A>G	p.Asn886Ser	missense_variant	18/18	ENST00000331968.11	NP_002733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKD1	ENST00000331968.11 linkuse as main transcript	c.2657A>G	p.Asn886Ser	missense_variant	18/18	1	NM_002742.3	ENSP00000333568	P3

Frequencies

GnomAD3 genomes

AF:

0.00578

AC:

880

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00142

AC:

357

AN:

250968

Hom.:

AF XY:

0.00111

AC XY:

150

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000588

AC:

860

AN:

1461604

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

372

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000756

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00578

AC:

880

AN:

152252

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0194

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.00627

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00188

AC:

228

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

PRKD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.093

DANN

Benign

0.71

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.71

T;.;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.44

.;N;N

REVEL

Benign

0.050

Sift

Benign

0.73

.;T;T

Sift4G

Benign

0.96

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.038

MVP

0.50

MPC

0.28

ClinPred

0.00024

GERP RS

-4.1

Varity_R

0.034

gMVP

0.28

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