Variant 17-4810949-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002663.5(PLD2):c.1008G>A(p.Arg336=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 1,608,582 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

PLD2
NM_002663.5 splice_region, synonymous

Scores

Splicing: ADA: 0.0004689

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

Variant links:

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]

PLD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 17-4810949-G-A is Benign according to our data. Variant chr17-4810949-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 732827.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD2	NM_002663.5 linkuse as main transcript	c.1008G>A	p.Arg336=	splice_region_variant, synonymous_variant	10/25	ENST00000263088.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD2	ENST00000263088.11 linkuse as main transcript	c.1008G>A	p.Arg336=	splice_region_variant, synonymous_variant	10/25	1	NM_002663.5	P1	O14939-1
PLD2	ENST00000572940.5 linkuse as main transcript	c.1008G>A	p.Arg336=	splice_region_variant, synonymous_variant	10/25	1			O14939-4
PLD2	ENST00000575813.5 linkuse as main transcript	c.144G>A	p.Arg48=	splice_region_variant, synonymous_variant, NMD_transcript_variant	1/4	4
PLD2	ENST00000575246.6 linkuse as main transcript	c.*656G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	10/18	2

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000595

AC:

146

AN:

245242

Hom.:

AF XY:

0.000655

AC XY:

AN XY:

132782

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000297

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.00103

AC:

1505

AN:

1456414

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

745

AN XY:

724502

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000902

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000384

Gnomad4 FIN exome

AF:

0.000379

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.000624

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000718

Hom.:

Bravo

AF:

0.000586

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

Cadd

Benign

Dann

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00047

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over