rs1052751

Variant names:

• chr17-4819490-G-A
• rs1052751
• NM_002663.5:c.2370G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-4819490-G-A
• chr17-4819490-G-C
• chr17-4819490-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002663.5(PLD2):​c.2370G>A​(p.Leu790Leu) 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLD2	NM_002663.5	c.2370G>A	p.Leu790Leu	synonymous_variant	Exon 23 of 25	ENST00000263088.11	NP_002654.3
PLD2	NM_001243108.2	c.2370G>A	p.Leu790Leu	synonymous_variant	Exon 23 of 25		NP_001230037.1
PLD2	XM_047436300.1	c.2010G>A	p.Leu670Leu	synonymous_variant	Exon 21 of 23		XP_047292256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.2370G>A	p.Leu790Leu	synonymous_variant	Exon 23 of 25	1	NM_002663.5	ENSP00000263088.5

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

GnomAD2 exomes AF: 0.143 AC: 35821 AN: 250894 AF XY: 0.142

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 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

African (AFR) AF: 0.110 AC: 3698 AN: 33480

American (AMR) AF: 0.145 AC: 6476 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4130 AN: 26126

East Asian (EAS) AF: 0.0575 AC: 2283 AN: 39698

South Asian (SAS) AF: 0.0980 AC: 8455 AN: 86240

European-Finnish (FIN) AF: 0.164 AC: 8770 AN: 53392

Middle Eastern (MID) AF: 0.167 AC: 963 AN: 5768

European-Non Finnish (NFE) AF: 0.175 AC: 194801 AN: 1111874

Other (OTH) AF: 0.152 AC: 9191 AN: 60388

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

African (AFR) AF: 0.119 AC: 4957 AN: 41516

American (AMR) AF: 0.153 AC: 2341 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3470

East Asian (EAS) AF: 0.0434 AC: 224 AN: 5166

South Asian (SAS) AF: 0.0930 AC: 448 AN: 4816

European-Finnish (FIN) AF: 0.167 AC: 1771 AN: 10604

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11867 AN: 67988

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.160 Hom.: 4453

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
PhyloP100		0.55
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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