chr17-4819581-G-A

Variant names:

• chr17-4819581-G-A
• rs3764897
• NM_002663.5:c.2461G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002663.5(PLD2):​c.2461G>A​(p.Gly821Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.161 in 1,605,654 control chromosomes in the GnomAD database, including 21,543 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 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 0.19 (2907 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18636 hom.)
• Consequence: PLD2 NM_002663.5 missense, splice_region
• Scores: Splicing: ADA: 0.0001024
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037055016).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD2	NM_002663.5	c.2461G>A	p.Gly821Ser	missense_variant, splice_region_variant	Exon 23 of 25	ENST00000263088.11	NP_002654.3
PLD2	XM_047436300.1	c.2101G>A	p.Gly701Ser	missense_variant, splice_region_variant	Exon 21 of 23		XP_047292256.1
PLD2	NM_001243108.2	c.2429+32G>A		intron_variant	Intron 23 of 24		NP_001230037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.2461G>A	p.Gly821Ser	missense_variant, splice_region_variant	Exon 23 of 25	1	NM_002663.5	ENSP00000263088.5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28576 AN: 151960 Hom.: 2903 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.153 AC: 37182 AN: 243770 AF XY: 0.149

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.0951

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.158 AC: 229759 AN: 1453576 Hom.: 18636 Cov.: 33 AF XY: 0.157 AC XY: 113612 AN XY: 722132

African (AFR) AF: 0.279 AC: 9332 AN: 33410

American (AMR) AF: 0.149 AC: 6613 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3649 AN: 25512

East Asian (EAS) AF: 0.112 AC: 4422 AN: 39608

South Asian (SAS) AF: 0.135 AC: 11515 AN: 85076

European-Finnish (FIN) AF: 0.131 AC: 6908 AN: 52888

Middle Eastern (MID) AF: 0.176 AC: 1009 AN: 5730

European-Non Finnish (NFE) AF: 0.160 AC: 176571 AN: 1107028

Other (OTH) AF: 0.162 AC: 9740 AN: 60082

GnomAD4 genome AF: 0.188 AC: 28616 AN: 152078 Hom.: 2907 Cov.: 31 AF XY: 0.186 AC XY: 13811 AN XY: 74344

African (AFR) AF: 0.280 AC: 11617 AN: 41474

American (AMR) AF: 0.173 AC: 2644 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3468

East Asian (EAS) AF: 0.103 AC: 531 AN: 5162

South Asian (SAS) AF: 0.126 AC: 607 AN: 4806

European-Finnish (FIN) AF: 0.131 AC: 1387 AN: 10604

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10755 AN: 67982

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.160 Hom.: 6899

Bravo AF: 0.196

TwinsUK AF: 0.155 AC: 574

ALSPAC AF: 0.159 AC: 613

ESP6500AA AF: 0.272 AC: 1198

ESP6500EA AF: 0.158 AC: 1363

ExAC AF: 0.154 AC: 18709

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.0	N
PhyloP100		4.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.17
Sift	Benign	0.81	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.074
MPC		0.14
ClinPred		0.010	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.30
Mutation Taster		=58/42	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.020
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: rs3764897; hg19: chr17-4722876; COSMIC: COSV54005726; COSMIC: COSV54005726;