2-218618690-G-T

Variant names:

• chr2-218618690-G-T
• rs761438839
• NM_032726.4:c.293G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032726.4(PLCD4):​c.293G>T​(p.Arg98Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R98C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.53

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.293G>T	p.Arg98Leu	missense_variant	Exon 4 of 16	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.293G>T	p.Arg98Leu	missense_variant	Exon 4 of 16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.293G>T	p.Arg98Leu	missense_variant	Exon 4 of 17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.293G>T	p.Arg98Leu	missense_variant	Exon 4 of 17	5		ENSP00000396942.1
PLCD4	ENST00000444453.5	n.190G>T		non_coding_transcript_exon_variant	Exon 4 of 5	4		ENSP00000415725.1
PLCD4	ENST00000446503.5	n.190G>T		non_coding_transcript_exon_variant	Exon 4 of 6	4		ENSP00000406040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Benign	0.96
DEOGEN2	Uncertain	0.70	D;D;.;D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.0	M;M;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.3	D;D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Uncertain	0.022	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.85
MutPred		0.70		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.88
MPC		0.93
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.62
gMVP		0.55

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: rs761438839; hg19: chr2-219483413;