Variant rs2286672 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.514C>T(p.Arg172Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,344 control chromosomes in the GnomAD database, including 14,533 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.089 ( 1233 hom., cov: 33)

Exomes 𝑓: 0.10 ( 13300 hom. )

Consequence

PLD2
NM_002663.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.716

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036799908).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD2	NM_002663.5 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	6/25	ENST00000263088.11	NP_002654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	6/25	1	NM_002663.5	ENSP00000263088	P1	O14939-1
PLD2	ENST00000572940.5 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	6/25	1		ENSP00000459571		O14939-4
PLD2	ENST00000575316.1 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	6/6	4		ENSP00000458795
PLD2	ENST00000575246.6 linkuse as main transcript	c.*162C>T		3_prime_UTR_variant, NMD_transcript_variant	6/18	2		ENSP00000459304

Frequencies

GnomAD3 genomes

AF:

0.0888

AC:

13506

AN:

152082

Hom.:

1240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0920

Gnomad EAS

AF:

0.406

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0738

GnomAD3 exomes

AF:

0.149

AC:

37465

AN:

251458

Hom.:

4624

AF XY:

0.156

AC XY:

21266

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.0774

Gnomad EAS exome

AF:

0.397

Gnomad SAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.0773

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.103

AC:

150494

AN:

1461144

Hom.:

13300

Cov.:

AF XY:

0.110

AC XY:

79884

AN XY:

726926

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.0805

Gnomad4 EAS exome

AF:

0.385

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.0731

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.0886

AC:

13491

AN:

152200

Hom.:

1233

Cov.:

AF XY:

0.0995

AC XY:

7402

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0920

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.0756

Gnomad4 OTH

AF:

0.0735

Alfa

AF:

0.0897

Hom.:

1419

Bravo

AF:

0.0767

TwinsUK

AF:

0.0731

AC:

271

ALSPAC

AF:

0.0669

AC:

258

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.0740

AC:

636

ExAC

AF:

0.147

AC:

17865

Asia WGS

AF:

0.359

AC:

1246

AN:

3478

EpiCase

AF:

0.0766

EpiControl

AF:

0.0778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.20

N;N;.

MutationTaster

Benign

0.029

P;P

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

D;.;.

REVEL

Benign

0.13

Sift

Benign

0.085

T;.;.

Sift4G

Uncertain

0.046

D;D;D

Polyphen

0.0

B;.;.

Vest4

0.060

MPC

0.19

ClinPred

0.017

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Varity_R

0.095

gMVP

0.36

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