17-4809548-G-A

Position:

• chr17-4809548-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002663.5(PLD2):​c.611G>A​(p.Gly204Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLD2 NM_002663.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.47

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD2	NM_002663.5	c.611G>A	p.Gly204Glu	missense_variant	7/25	ENST00000263088.11	NP_002654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD2	ENST00000263088.11	c.611G>A	p.Gly204Glu	missense_variant	7/25	1	NM_002663.5	ENSP00000263088	P1
PLD2	ENST00000572940.5	c.611G>A	p.Gly204Glu	missense_variant	7/25	1		ENSP00000459571
PLD2	ENST00000575246.6	c.*259G>A		3_prime_UTR_variant, NMD_transcript_variant	7/18	2		ENSP00000459304

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2024

The c.611G>A (p.G204E) alteration is located in exon 7 (coding exon 6) of the PLD2 gene. This alteration results from a G to A substitution at nucleotide position 611, causing the glycine (G) at amino acid position 204 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Uncertain	0.61
Sift	Uncertain	0.0070	D;.
Sift4G	Uncertain	0.030	D;D
Polyphen		1.0	D;.
Vest4		0.76
MutPred		0.58		Loss of MoRF binding (P = 0.0375);Loss of MoRF binding (P = 0.0375);
MVP		0.74
MPC		0.70
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.67
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4712843; COSMIC: COSV99562234; COSMIC: COSV99562234;