Genetic Variant PLD2:p.Gly821Arg (chr17-4819581-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002663.5(PLD2):c.2461G>C(p.Gly821Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000374 in 1,605,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PLD2
NM_002663.5 missense, splice_region

Scores

Splicing: ADA: 0.000005813

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.12

Publications

27 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058534592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002663.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD2	NM_002663.5	MANE Select	c.2461G>C	p.Gly821Arg	missense splice_region	Exon 23 of 25	NP_002654.3
	PLD2	NM_001243108.2		c.2429+32G>C		intron	N/A	NP_001230037.1	O14939-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLD2	ENST00000263088.11	TSL:1 MANE Select	c.2461G>C	p.Gly821Arg	missense splice_region	Exon 23 of 25	ENSP00000263088.5	O14939-1
PLD2	ENST00000572940.5	TSL:1	c.2429+32G>C		intron	N/A	ENSP00000459571.1	O14939-4
PLD2	ENST00000964340.1		c.2518G>C	p.Gly840Arg	missense splice_region	Exon 23 of 25	ENSP00000634399.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

243770

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1453926

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25520

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1107274

Other (OTH)

AF:

0.00

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41364

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

6899

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.069

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

M_CAP

Benign

0.0094

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.5

PhyloP100

4.1

PrimateAI

Uncertain

0.58

PROVEAN

Benign

3.8

REVEL

Uncertain

0.33

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.27

MutPred

0.20

Gain of MoRF binding (P = 0.0064)

MVP

0.36

MPC

0.16

ClinPred

0.057

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.44

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000058

dbscSNV1_RF

Benign

0.042

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over