chr2-218636381-G-T

Position:

• chr2-218636381-G-T

Variant summary

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

The NM_032726.4(PLCD4):​c.2171G>T​(p.Cys724Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86

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]

ZNF142 (HGNC:12927): (zinc finger protein 142) The protein encoded by this gene belongs to the Kruppel family of C2H2-type zinc finger proteins. It contains 31 C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

PLCD4 (HGNC:):

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	Protein	UniProt
PLCD4	NM_032726.4	c.2171G>T	p.Cys724Phe	missense_variant	15/16	ENST00000450993.7	NP_116115.1
ZNF142	NM_001379659.1	c.*1958C>A		3_prime_UTR_variant	11/11	ENST00000411696.7	NP_001366588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.2171G>T	p.Cys724Phe	missense_variant	15/16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.2267G>T	p.Cys756Phe	missense_variant	16/17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.2171G>T	p.Cys724Phe	missense_variant	15/17	5		ENSP00000396942.1
ZNF142	ENST00000411696	c.*1958C>A		3_prime_UTR_variant	11/11	5	NM_001379659.1	ENSP00000398798.3

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

Aug 27, 2024

The c.2171G>T (p.C724F) alteration is located in exon 15 (coding exon 14) of the PLCD4 gene. This alteration results from a G to T substitution at nucleotide position 2171, causing the cysteine (C) at amino acid position 724 to be replaced by a phenylalanine (F). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D;D;D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.54
MutPred		0.55		Loss of catalytic residue at C724 (P = 0.0494);Loss of catalytic residue at C724 (P = 0.0494);.;
MVP		0.55
MPC		1.0
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.60
gMVP		0.61

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: chr2-219501104;