2-218622858-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032726.4(PLCD4):c.752G>A(p.Arg251His) variant causes a missense change. The variant allele was found at a frequency of 0.0000868 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
PLCD4
NM_032726.4 missense
NM_032726.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.70
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026826143).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCD4 | NM_032726.4 | c.752G>A | p.Arg251His | missense_variant | 6/16 | ENST00000450993.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCD4 | ENST00000450993.7 | c.752G>A | p.Arg251His | missense_variant | 6/16 | 1 | NM_032726.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000120 AC: 30AN: 248984Hom.: 0 AF XY: 0.0000962 AC XY: 13AN XY: 135092
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461398Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 726984
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GnomAD4 genome AF: 0.000269 AC: 41AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74478
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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 | May 15, 2024 | The c.752G>A (p.R251H) alteration is located in exon 6 (coding exon 5) of the PLCD4 gene. This alteration results from a G to A substitution at nucleotide position 752, causing the arginine (R) at amino acid position 251 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;T;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at