rs1052751

chr17-4819490-G-Achr17-4819490-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002663.5(PLD2):c.2370G>A(p.Leu790=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,798 control chromosomes in the GnomAD database, including 21,822 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1795 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20027 hom.)
• Consequence: PLD2 NM_002663.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.549 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD2	NM_002663.5	c.2370G>A	p.Leu790=	synonymous_variant	23/25	ENST00000263088.11
PLD2	NM_001243108.2	c.2370G>A	p.Leu790=	synonymous_variant	23/25
PLD2	XM_047436300.1	c.2010G>A	p.Leu670=	synonymous_variant	21/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD2	ENST00000263088.11	c.2370G>A	p.Leu790=	synonymous_variant	23/25	1	NM_002663.5	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22619 AN: 152030 Hom.: 1793 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.143 AC: 35821 AN: 250894 Hom.: 2750 AF XY: 0.142 AC XY: 19273 AN XY: 135658

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0381

Gnomad SAS exome AF: 0.0966

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.163 AC: 238767 AN: 1461650 Hom.: 20027 Cov.: 34 AF XY: 0.162 AC XY: 117502 AN XY: 727110

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.0575

Gnomad4 SAS exome AF: 0.0980

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.149 AC: 22637 AN: 152148 Hom.: 1795 Cov.: 31 AF XY: 0.148 AC XY: 11047 AN XY: 74394

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.0930

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.161

Alfa AF: 0.161 Hom.: 3395

Bravo AF: 0.145

Asia WGS AF: 0.0930 AC: 325 AN: 3478

EpiCase AF: 0.171

EpiControl AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	6.4
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs1052751; hg19: chr17-4722785; COSMIC: COSV54004613; COSMIC: COSV54004613;