2-218633684-A-C

Position:

• chr2-218633684-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032726.4(PLCD4):​c.1529A>C​(p.His510Pro) 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. 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: 5.24

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3960672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.1529A>C	p.His510Pro	missense_variant	11/16	ENST00000450993.7	NP_116115.1
ZNF142	NM_001379659.1	c.*4655T>G		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.1529A>C	p.His510Pro	missense_variant	11/16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.1625A>C	p.His542Pro	missense_variant	12/17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.1529A>C	p.His510Pro	missense_variant	11/17	5		ENSP00000396942.1
ZNF142	ENST00000411696	c.*4655T>G		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 26, 2024

The c.1529A>C (p.H510P) alteration is located in exon 11 (coding exon 10) of the PLCD4 gene. This alteration results from a A to C substitution at nucleotide position 1529, causing the histidine (H) at amino acid position 510 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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Benign	0.80
DEOGEN2	Uncertain	0.53	D;D;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.69	T;.;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.9	M;M;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.62	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.26
MutPred		0.40		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;
MVP		0.84
MPC		1.0
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr2-219498407;