rs1052748

Positions:

• chr17-4817174-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002663.5(PLD2):​c.1730C>T​(p.Thr577Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,611,076 control chromosomes in the GnomAD database, including 165,709 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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.

• Frequency:
  • Genomes: 𝑓 0.36 (11292 hom., cov: 31)
  • Exomes 𝑓: 0.45 (154417 hom.)
• Consequence: PLD2 NM_002663.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=6.7296624E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD2	NM_002663.5	c.1730C>T	p.Thr577Ile	missense_variant	17/25	ENST00000263088.11	NP_002654.3
PLD2	NM_001243108.2	c.1730C>T	p.Thr577Ile	missense_variant	17/25		NP_001230037.1
PLD2	XM_047436300.1	c.1370C>T	p.Thr457Ile	missense_variant	15/23		XP_047292256.1
PLD2	XM_047436301.1	c.1681C>T	p.His561Tyr	missense_variant	16/19		XP_047292257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.1730C>T	p.Thr577Ile	missense_variant	17/25	1	NM_002663.5	ENSP00000263088	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54095 AN: 151880 Hom.: 11284 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.393 AC: 98787 AN: 251392 Hom.: 21601 AF XY: 0.396 AC XY: 53862 AN XY: 135882

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.310

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.449 AC: 655217 AN: 1459080 Hom.: 154417 Cov.: 35 AF XY: 0.446 AC XY: 324160 AN XY: 726024

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.356 AC: 54141 AN: 151996 Hom.: 11292 Cov.: 31 AF XY: 0.348 AC XY: 25822 AN XY: 74290

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.381

Alfa AF: 0.452 Hom.: 27613

Bravo AF: 0.354

TwinsUK AF: 0.481 AC: 1784

ALSPAC AF: 0.492 AC: 1898

ESP6500AA AF: 0.167 AC: 735

ESP6500EA AF: 0.481 AC: 4136

ExAC AF: 0.392 AC: 47638

Asia WGS AF: 0.214 AC: 748 AN: 3478

EpiCase AF: 0.478

EpiControl AF: 0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0050
DANN	Benign	0.43
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.15	T;T;T
MetaRNN	Benign	0.00067	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.75	N;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N;.;.
REVEL	Benign	0.017
Sift	Benign	0.25	T;.;.
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.088
MPC		0.15
ClinPred		0.034	T
GERP RS		-9.0
Varity_R		0.11
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1052748; hg19: chr17-4720469; COSMIC: COSV54007900; COSMIC: COSV54007900;