chr2-218633716-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032726.4(PLCD4):ā€‹c.1561T>Cā€‹(p.Ser521Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000051 ( 0 hom. )

Consequence

PLCD4
NM_032726.4 missense

Scores

3
13
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLCD4NM_032726.4 linkuse as main transcriptc.1561T>C p.Ser521Pro missense_variant 11/16 ENST00000450993.7
ZNF142NM_001379659.1 linkuse as main transcriptc.*4623A>G 3_prime_UTR_variant 11/11 ENST00000411696.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLCD4ENST00000450993.7 linkuse as main transcriptc.1561T>C p.Ser521Pro missense_variant 11/161 NM_032726.4 P1Q9BRC7-1
ZNF142ENST00000411696.7 linkuse as main transcriptc.*4623A>G 3_prime_UTR_variant 11/115 NM_001379659.1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000763
AC:
19
AN:
249132
Hom.:
0
AF XY:
0.000104
AC XY:
14
AN XY:
135186
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000620
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000513
AC:
75
AN:
1461694
Hom.:
0
Cov.:
31
AF XY:
0.0000578
AC XY:
42
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000910
AC:
11
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsApr 19, 2024The c.1561T>C (p.S521P) alteration is located in exon 11 (coding exon 10) of the PLCD4 gene. This alteration results from a T to C substitution at nucleotide position 1561, causing the serine (S) at amino acid position 521 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
0.80
BayesDel_addAF
Benign
-0.098
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
D;D;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;.;T
M_CAP
Benign
0.061
D
MetaRNN
Pathogenic
0.88
D;D;D
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Uncertain
2.7
M;M;.
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.024
D;D;D
Polyphen
0.99
D;D;.
Vest4
0.86
MutPred
0.75
Loss of phosphorylation at S521 (P = 0.0869);Loss of phosphorylation at S521 (P = 0.0869);.;
MVP
0.76
MPC
0.91
ClinPred
0.76
D
GERP RS
4.2
Varity_R
0.80
gMVP
0.82

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.

Other links and lift over

dbSNP: rs751900322; hg19: chr2-219498439; COSMIC: COSV68745742; COSMIC: COSV68745742; API