rs1052748

Variant names:

• chr17-4817174-C-T
• rs1052748
• NM_002663.5:c.1730C>T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 55 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=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 rank	MANE	Protein	UniProt
PLD2	NM_002663.5	c.1730C>T	p.Thr577Ile	missense_variant	Exon 17 of 25	ENST00000263088.11	NP_002654.3
PLD2	NM_001243108.2	c.1730C>T	p.Thr577Ile	missense_variant	Exon 17 of 25		NP_001230037.1
PLD2	XM_047436300.1	c.1370C>T	p.Thr457Ile	missense_variant	Exon 15 of 23		XP_047292256.1
PLD2	XM_047436301.1	c.1681C>T	p.His561Tyr	missense_variant	Exon 16 of 19		XP_047292257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.1730C>T	p.Thr577Ile	missense_variant	Exon 17 of 25	1	NM_002663.5	ENSP00000263088.5

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

GnomAD2 exomes AF: 0.393 AC: 98787 AN: 251392 AF XY: 0.396

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 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

African (AFR) AF: 0.138 AC: 4615 AN: 33460

American (AMR) AF: 0.415 AC: 18557 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 11087 AN: 26122

East Asian (EAS) AF: 0.114 AC: 4523 AN: 39692

South Asian (SAS) AF: 0.316 AC: 27255 AN: 86204

European-Finnish (FIN) AF: 0.376 AC: 20104 AN: 53400

Middle Eastern (MID) AF: 0.371 AC: 2137 AN: 5762

European-Non Finnish (NFE) AF: 0.489 AC: 542200 AN: 1109398

Other (OTH) AF: 0.410 AC: 24739 AN: 60322

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

African (AFR) AF: 0.155 AC: 6444 AN: 41496

American (AMR) AF: 0.394 AC: 6007 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1459 AN: 3468

East Asian (EAS) AF: 0.107 AC: 554 AN: 5178

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4816

European-Finnish (FIN) AF: 0.360 AC: 3802 AN: 10562

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33070 AN: 67912

Other (OTH) AF: 0.381 AC: 804 AN: 2110

Alfa AF: 0.442 Hom.: 53800

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;.
PhyloP100		-1.5
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
PromoterAI		-0.021	Neutral
Varity_R		0.11
gMVP		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1052748; hg19: chr17-4720469; COSMIC: COSV54007900; COSMIC: COSV54007900;