chr17-4809322-C-T

Position:

• chr17-4809322-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.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. 12/20 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 0.089 (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

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=0.0036799908).
• 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/exons	MANE	Protein	UniProt
PLD2	NM_002663.5	c.514C>T	p.Arg172Cys	missense_variant	6/25	ENST00000263088.11	NP_002654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.514C>T	p.Arg172Cys	missense_variant	6/25	1	NM_002663.5	ENSP00000263088	P1
PLD2	ENST00000572940.5	c.514C>T	p.Arg172Cys	missense_variant	6/25	1		ENSP00000459571
PLD2	ENST00000575316.1	c.514C>T	p.Arg172Cys	missense_variant	6/6	4		ENSP00000458795
PLD2	ENST00000575246.6	c.*162C>T		3_prime_UTR_variant, NMD_transcript_variant	6/18	2		ENSP00000459304

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

GnomAD3 exomes AF: 0.149 AC: 37465 AN: 251458 Hom.: 4624 AF XY: 0.156 AC XY: 21266 AN XY: 135910

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 SAS exome AF: 0.349

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

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.0805

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0731

Gnomad4 OTH exome AF: 0.113

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

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0897 Hom.: 1419

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;.
MutationTaster	Benign	0.029	P;P
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

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: rs2286672; hg19: chr17-4712617; COSMIC: COSV54005632; COSMIC: COSV54005632;