Variant 17-4808013-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002663.5(PLD2):c.139T>A(p.Tyr47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,611,572 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

PLD2
NM_002663.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054072767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD2	NM_002663.5 linkuse as main transcript	c.139T>A	p.Tyr47Asn	missense_variant	3/25	ENST00000263088.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD2	ENST00000263088.11 linkuse as main transcript	c.139T>A	p.Tyr47Asn	missense_variant	3/25	1	NM_002663.5	P1	O14939-1

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000450

AC:

113

AN:

251234

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.000783

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000602

AC:

879

AN:

1459308

Hom.:

Cov.:

AF XY:

0.000576

AC XY:

418

AN XY:

725352

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.000720

Gnomad4 OTH exome

AF:

0.000581

GnomAD4 genome

AF:

0.000368

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000426

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000544

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000296

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

Jan 03, 2022

The c.139T>A (p.Y47N) alteration is located in exon 3 (coding exon 2) of the PLD2 gene. This alteration results from a T to A substitution at nucleotide position 139, causing the tyrosine (Y) at amino acid position 47 to be replaced by an asparagine (N). 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

Benign

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.52

D;.;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

M;M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.6

D;.;.

REVEL

Benign

0.17

Sift

Benign

0.033

D;.;.

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.75

P;.;.

Vest4

0.78

MVP

0.72

MPC

0.68

ClinPred

0.13

GERP RS

5.2

Varity_R

0.43

gMVP

0.80

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