chr2-218615966-T-C

Position:

• chr2-218615966-T-C

Variant summary

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

The NM_032726.4(PLCD4):​c.85T>C​(p.Ser29Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCD4	NM_032726.4	c.85T>C	p.Ser29Pro	missense_variant	3/16	ENST00000450993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCD4	ENST00000450993.7	c.85T>C	p.Ser29Pro	missense_variant	3/16	1	NM_032726.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 07, 2023

The c.85T>C (p.S29P) alteration is located in exon 3 (coding exon 2) of the PLCD4 gene. This alteration results from a T to C substitution at nucleotide position 85, causing the serine (S) at amino acid position 29 to be replaced by a proline (P). 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	0.81
BayesDel_addAF	Benign	-0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;D;.;D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;.;T;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.6	M;M;.;.
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.069	T;T;D;D
Sift4G	Benign	0.077	T;T;D;T
Polyphen		1.0	D;D;.;.
Vest4		0.42
MutPred		0.48		Gain of glycosylation at S29 (P = 0.0218);Gain of glycosylation at S29 (P = 0.0218);Gain of glycosylation at S29 (P = 0.0218);Gain of glycosylation at S29 (P = 0.0218);
MVP		0.83
MPC		0.89
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.58
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-219480689;