Variant 17-4810930-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002663.5(PLD2):c.989G>A(p.Arg330Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00349 in 1,612,050 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R330W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 19 hom. )

Consequence

PLD2
NM_002663.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.15

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076674223).

BP6

Variant 17-4810930-G-A is Benign according to our data. Variant chr17-4810930-G-A is described in ClinVar as [Benign]. Clinvar id is 713669.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD2	NM_002663.5 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	10/25	ENST00000263088.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD2	ENST00000263088.11 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	10/25	1	NM_002663.5	P1	O14939-1
PLD2	ENST00000572940.5 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	10/25	1			O14939-4
PLD2	ENST00000575813.5 linkuse as main transcript	c.125G>A	p.Arg42Gln	missense_variant, NMD_transcript_variant	1/4	4
PLD2	ENST00000575246.6 linkuse as main transcript	c.*637G>A		3_prime_UTR_variant, NMD_transcript_variant	10/18	2

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

478

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00313

AC:

777

AN:

248444

Hom.:

AF XY:

0.00314

AC XY:

422

AN XY:

134338

show subpopulations

Gnomad AFR exome

AF:

0.000926

Gnomad AMR exome

AF:

0.000671

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00230

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00355

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00353

AC:

5146

AN:

1459848

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

2520

AN XY:

726222

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.000695

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.00365

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00314

AC:

478

AN:

152202

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

275

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00317

Hom.:

Bravo

AF:

0.00233

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00315

AC:

383

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00374

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.18

Sift

Benign

0.19

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.22

B;.

Vest4

0.28

MVP

0.48

MPC

0.21

ClinPred

0.035

GERP RS

5.1

Varity_R

0.51

gMVP

0.88

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