Variant chr2-218615954-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032726.4(PLCD4):c.73C>T(p.Arg25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

PLCD4
NM_032726.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

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]

PLCD4 links:

PLCD4 (HGNC:):

PLCD4 links:

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ACMG classification

Classification made for transcript

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=0.2677815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCD4	NM_032726.4 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	3/16	ENST00000450993.7	NP_116115.1	Q9BRC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLCD4	ENST00000450993.7 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	3/16	1	NM_032726.4	ENSP00000388631.2	Q9BRC7-1
PLCD4	ENST00000432688.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	3/17	5		ENSP00000396185.1	C9JEA7
PLCD4	ENST00000417849.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	3/17	5		ENSP00000396942.1	Q9BRC7-1
PLCD4	ENST00000444453.5 linkuse as main transcript	n.73C>T		non_coding_transcript_exon_variant	3/5	4		ENSP00000415725.1	F2Z3H8
PLCD4	ENST00000446503.5 linkuse as main transcript	n.73C>T		non_coding_transcript_exon_variant	3/6	4		ENSP00000406040.1	F2Z3H8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249250

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.73C>T (p.R25C) alteration is located in exon 3 (coding exon 2) of the PLCD4 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the arginine (R) at amino acid position 25 to be replaced by a cysteine (C). 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

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Benign

0.82

DEOGEN2

Uncertain

0.44

T;T;.;D

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

T;.;D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.6

L;L;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.5

D;D;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.18

T;T;D;T

Polyphen

1.0

D;D;.;.

Vest4

0.48

MVP

0.73

MPC

0.97

ClinPred

0.64

GERP RS

3.2

Varity_R

0.11

gMVP

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over