Genetic Variant PLCD4:p.Arg25Pro (chr2-218615955-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032726.4(PLCD4):c.74G>C(p.Arg25Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R25C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PLCD4
NM_032726.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.68

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4 link	c.74G>C	p.Arg25Pro	missense_variant	Exon 3 of 16	ENST00000450993.7	NP_116115.1	Q9BRC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLCD4	ENST00000450993.7 link	c.74G>C	p.Arg25Pro	missense_variant	Exon 3 of 16	1	NM_032726.4	ENSP00000388631.2	Q9BRC7-1
PLCD4	ENST00000432688.5 link	c.74G>C	p.Arg25Pro	missense_variant	Exon 3 of 17	5		ENSP00000396185.1	C9JEA7
PLCD4	ENST00000417849.5 link	c.74G>C	p.Arg25Pro	missense_variant	Exon 3 of 17	5		ENSP00000396942.1	Q9BRC7-1
PLCD4	ENST00000444453.5 link	n.74G>C		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000415725.1	F2Z3H8
PLCD4	ENST00000446503.5 link	n.74G>C		non_coding_transcript_exon_variant	Exon 3 of 6	4		ENSP00000406040.1	F2Z3H8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111868

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Benign

0.80

DEOGEN2

Uncertain

0.80

D;D;.;D

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;.;T;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.6

M;M;.;.

PhyloP100

7.7

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Uncertain

0.44

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.20

T;T;D;T

Polyphen

1.0

D;D;.;.

Vest4

0.81

MutPred

0.60

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MVP

0.74

MPC

1.0

ClinPred

0.98

GERP RS

3.2

Varity_R

0.50

gMVP

0.92

Mutation Taster

=56/44

polymorphism

(source)

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

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chr2-218615955-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over