chr2-218618798-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032726.4(PLCD4):​c.401G>A​(p.Arg134His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,587,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

PLCD4
NM_032726.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.770
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20757428).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLCD4NM_032726.4 linkuse as main transcriptc.401G>A p.Arg134His missense_variant 4/16 ENST00000450993.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLCD4ENST00000450993.7 linkuse as main transcriptc.401G>A p.Arg134His missense_variant 4/161 NM_032726.4 P1Q9BRC7-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000444
AC:
9
AN:
202878
Hom.:
0
AF XY:
0.0000183
AC XY:
2
AN XY:
109068
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000408
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000227
Gnomad OTH exome
AF:
0.000189
GnomAD4 exome
AF:
0.0000293
AC:
42
AN:
1435544
Hom.:
0
Cov.:
31
AF XY:
0.0000295
AC XY:
21
AN XY:
711624
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000493
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000191
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000119
AC:
1
ExAC
AF:
0.0000332
AC:
4

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 GeneticsDec 27, 2022The c.401G>A (p.R134H) alteration is located in exon 4 (coding exon 3) of the PLCD4 gene. This alteration results from a G to A substitution at nucleotide position 401, causing the arginine (R) at amino acid position 134 to be replaced by a histidine (H). 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
0.075
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.55
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.52
D;D;T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.88
D;.;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.6
L;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Benign
0.068
Sift
Uncertain
0.020
D;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
0.98
D;D;.
Vest4
0.41
MVP
0.67
MPC
0.54
ClinPred
0.41
T
GERP RS
1.7
Varity_R
0.068
gMVP
0.18

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

LitVar

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

Other links and lift over

dbSNP: rs200972923; hg19: chr2-219483521; API