chr2-218622858-G-T

Variant names:

• chr2-218622858-G-T
• rs184719765
• NM_032726.4:c.752G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032726.4(PLCD4):​c.752G>T​(p.Arg251Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. R251H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2577445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.752G>T	p.Arg251Leu	missense_variant	Exon 6 of 16	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.752G>T	p.Arg251Leu	missense_variant	Exon 6 of 16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.752G>T	p.Arg251Leu	missense_variant	Exon 6 of 17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.752G>T	p.Arg251Leu	missense_variant	Exon 6 of 17	5		ENSP00000396942.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D;D;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	M;M;.
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.17
Sift	Benign	0.063	T;T;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.0070	B;B;.
Vest4		0.24
MutPred		0.47		Gain of catalytic residue at R251 (P = 0.0198);Gain of catalytic residue at R251 (P = 0.0198);Gain of catalytic residue at R251 (P = 0.0198);
MVP		0.50
MPC		0.28
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.27
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs184719765; hg19: chr2-219487581;