rs2286672

Variant names:

• chr17-4809322-C-T
• rs2286672
• NM_002663.5:c.514C>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.514C>T​(p.Arg172Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,344 control chromosomes in the GnomAD database, including 14,533 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.089 (1233 hom., cov: 33)
  • Exomes 𝑓: 0.10 (13300 hom.)
• Consequence: PLD2 NM_002663.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 63 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=0.0036799908).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD2	NM_002663.5	c.514C>T	p.Arg172Cys	missense_variant	Exon 6 of 25	ENST00000263088.11	NP_002654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.514C>T	p.Arg172Cys	missense_variant	Exon 6 of 25	1	NM_002663.5	ENSP00000263088.5

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13506 AN: 152082 Hom.: 1240 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0738

GnomAD2 exomes AF: 0.149 AC: 37465 AN: 251458 AF XY: 0.156

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.0774

Gnomad EAS exome AF: 0.397

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.0773

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.103 AC: 150494 AN: 1461144 Hom.: 13300 Cov.: 35 AF XY: 0.110 AC XY: 79884 AN XY: 726926

African (AFR) AF: 0.0125 AC: 420 AN: 33474

American (AMR) AF: 0.155 AC: 6910 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 2104 AN: 26134

East Asian (EAS) AF: 0.385 AC: 15268 AN: 39688

South Asian (SAS) AF: 0.339 AC: 29198 AN: 86198

European-Finnish (FIN) AF: 0.148 AC: 7916 AN: 53396

Middle Eastern (MID) AF: 0.100 AC: 577 AN: 5764

European-Non Finnish (NFE) AF: 0.0731 AC: 81277 AN: 1111404

Other (OTH) AF: 0.113 AC: 6824 AN: 60364

GnomAD4 genome AF: 0.0886 AC: 13491 AN: 152200 Hom.: 1233 Cov.: 33 AF XY: 0.0995 AC XY: 7402 AN XY: 74408

African (AFR) AF: 0.0177 AC: 736 AN: 41556

American (AMR) AF: 0.105 AC: 1600 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 319 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2090 AN: 5146

South Asian (SAS) AF: 0.356 AC: 1716 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1706 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5140 AN: 67996

Other (OTH) AF: 0.0735 AC: 155 AN: 2110

Alfa AF: 0.0880 Hom.: 2055

Bravo AF: 0.0767

TwinsUK AF: 0.0731 AC: 271

ALSPAC AF: 0.0669 AC: 258

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.0740 AC: 636

ExAC AF: 0.147 AC: 17865

Asia WGS AF: 0.359 AC: 1246 AN: 3478

EpiCase AF: 0.0766

EpiControl AF: 0.0778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.88	D;D;D
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.20	N;N;.
PhyloP100		0.72
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D;.;.
REVEL	Benign	0.13
Sift	Benign	0.085	T;.;.
Sift4G	Uncertain	0.046	D;D;D
Polyphen		0.0	B;.;.
Vest4		0.060
MPC		0.19
ClinPred		0.017	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Varity_R		0.095
gMVP		0.36
Mutation Taster		=96/4	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: rs2286672; hg19: chr17-4712617; COSMIC: COSV54005632; COSMIC: COSV54005632;