rs3764897

Positions:

• chr17-4819581-G-A
• chr17-4819581-G-C

Variant summary

Our verdict is Benign. Variant got -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. 14/22 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G821R) has been classified as Likely benign.

• 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

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 -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/exons	MANE	Protein	UniProt
PLD2	NM_002663.5	c.2461G>A	p.Gly821Ser	missense_variant, splice_region_variant	23/25	ENST00000263088.11	NP_002654.3
PLD2	XM_047436300.1	c.2101G>A	p.Gly701Ser	missense_variant, splice_region_variant	21/23		XP_047292256.1
PLD2	NM_001243108.2	c.2429+32G>A		intron_variant			NP_001230037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.2461G>A	p.Gly821Ser	missense_variant, splice_region_variant	23/25	1	NM_002663.5	ENSP00000263088.5
PLD2	ENST00000572940.5	c.2429+32G>A		intron_variant		1		ENSP00000459571.1
PLD2	ENST00000576864.1	c.352G>A	p.Gly118Ser	missense_variant, splice_region_variant	4/7	3		ENSP00000460477.1

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

GnomAD3 exomes AF: 0.153 AC: 37182 AN: 243770 Hom.: 3054 AF XY: 0.149 AC XY: 19597 AN XY: 131510

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 SAS exome AF: 0.136

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

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.162

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

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.189

Alfa AF: 0.151 Hom.: 2698

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764897; hg19: chr17-4722876; COSMIC: COSV54005726; COSMIC: COSV54005726;