17-4810001-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002663.5(PLD2):c.832C>T(p.His278Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,566 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (8 hom.)
• Consequence: PLD2 NM_002663.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00864616).
• BP6: Variant 17-4810001-C-T is Benign according to our data. Variant chr17-4810001-C-T is described in ClinVar as [Benign]. Clinvar id is 780392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00586 (892/152268) while in subpopulation AFR AF= 0.0193 (802/41570). AF 95% confidence interval is 0.0182. There are 10 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD2	NM_002663.5	c.832C>T	p.His278Tyr	missense_variant	9/25	ENST00000263088.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD2	ENST00000263088.11	c.832C>T	p.His278Tyr	missense_variant	9/25	1	NM_002663.5	P1
PLD2	ENST00000572940.5	c.832C>T	p.His278Tyr	missense_variant	9/25	1
PLD2	ENST00000575246.6	c.*480C>T		3_prime_UTR_variant, NMD_transcript_variant	9/18	2

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152150 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00175 AC: 441 AN: 251342 Hom.: 7 AF XY: 0.00120 AC XY: 163 AN XY: 135866

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000721 AC: 1053 AN: 1461298 Hom.: 8 Cov.: 33 AF XY: 0.000623 AC XY: 453 AN XY: 726960

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000167

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00586 AC: 892 AN: 152268 Hom.: 10 Cov.: 32 AF XY: 0.00555 AC XY: 413 AN XY: 74452

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00103 Hom.: 4

Bravo AF: 0.00642

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0179 AC: 79

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00195 AC: 237

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	11
Dann	Benign	0.78
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.11	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.080
Sift	Benign	0.27	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.23
MVP		0.33
MPC		0.16
ClinPred		0.0051	T
GERP RS		4.9
Varity_R		0.031
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs139166795; hg19: chr17-4713296;