NM_002663.5:c.71C>G

Variant names:

• chr17-4807843-C-G
• rs1404278136
• NM_002663.5:c.71C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002663.5(PLD2):​c.71C>G​(p.Ser24Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S24F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PLD2 NM_002663.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08950612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002663.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD2	NM_002663.5	MANE Select	c.71C>G	p.Ser24Cys	missense	Exon 2 of 25	NP_002654.3
	PLD2	NM_001243108.2		c.71C>G	p.Ser24Cys	missense	Exon 2 of 25	NP_001230037.1	O14939-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD2	ENST00000263088.11	TSL:1 MANE Select	c.71C>G	p.Ser24Cys	missense	Exon 2 of 25	ENSP00000263088.5	O14939-1
	PLD2	ENST00000572940.5	TSL:1	c.71C>G	p.Ser24Cys	missense	Exon 2 of 25	ENSP00000459571.1	O14939-4
	PLD2	ENST00000964340.1		c.71C>G	p.Ser24Cys	missense	Exon 2 of 25	ENSP00000634399.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.059
Sift	Benign	0.037	D
Sift4G	Uncertain	0.050	T
Polyphen		0.26	B
Vest4		0.22
MutPred		0.27		Gain of catalytic residue at M22 (P = 8e-04)
MVP		0.50
MPC		0.23
ClinPred		0.47	T
GERP RS		5.1
PromoterAI		-0.0017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.25

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

Other links and lift over

dbSNP: rs1404278136; hg19: chr17-4711138;