Variant 17-4817174-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002663.5(PLD2):c.1730C>T(p.Thr577Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,611,076 control chromosomes in the GnomAD database, including 165,709 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 11292 hom., cov: 31)

Exomes 𝑓: 0.45 ( 154417 hom. )

Consequence

PLD2
NM_002663.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Variant links:

Genes affected

PLD2 (HGNC:9068): (phospholipase D2) The protein encoded by this gene catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline. The activity of the encoded enzyme is enhanced by phosphatidylinositol 4,5-bisphosphate and ADP-ribosylation factor-1. This protein localizes to the peripheral membrane and may be involved in cytoskeletal organization, cell cycle control, transcriptional regulation, and/or regulated secretion. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

PLD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.7296624E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLD2	NM_002663.5 linkuse as main transcript	c.1730C>T	p.Thr577Ile	missense_variant	17/25	ENST00000263088.11
PLD2	NM_001243108.2 linkuse as main transcript	c.1730C>T	p.Thr577Ile	missense_variant	17/25
PLD2	XM_047436300.1 linkuse as main transcript	c.1370C>T	p.Thr457Ile	missense_variant	15/23
PLD2	XM_047436301.1 linkuse as main transcript	c.1681C>T	p.His561Tyr	missense_variant	16/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD2	ENST00000263088.11 linkuse as main transcript	c.1730C>T	p.Thr577Ile	missense_variant	17/25	1	NM_002663.5	P1	O14939-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54095

AN:

151880

Hom.:

11284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.393

AC:

98787

AN:

251392

Hom.:

21601

AF XY:

0.396

AC XY:

53862

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.449

AC:

655217

AN:

1459080

Hom.:

154417

Cov.:

AF XY:

0.446

AC XY:

324160

AN XY:

726024

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.415

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.489

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.356

AC:

54141

AN:

151996

Hom.:

11292

Cov.:

AF XY:

0.348

AC XY:

25822

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.381

Alfa

AF:

0.452

Hom.:

27613

Bravo

AF:

0.354

TwinsUK

AF:

0.481

AC:

1784

ALSPAC

AF:

0.492

AC:

1898

ESP6500AA

AF:

0.167

AC:

735

ESP6500EA

AF:

0.481

AC:

4136

ExAC

AF:

0.392

AC:

47638

Asia WGS

AF:

0.214

AC:

748

AN:

3478

EpiCase

AF:

0.478

EpiControl

AF:

0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0050

DANN

Benign

0.43

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.15

T;T;T

MetaRNN

Benign

0.00067

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.75

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.1

N;.;.

REVEL

Benign

0.017

Sift

Benign

0.25

T;.;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.088

MPC

0.15

ClinPred

0.034

GERP RS

-9.0

Varity_R

0.11

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over