chr2-218628139-C-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_032726.4(PLCD4):c.883C>A(p.Pro295Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,613,916 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 (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
PLCD4
NM_032726.4 missense
NM_032726.4 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 6.09
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_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.973
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCD4 | NM_032726.4 | c.883C>A | p.Pro295Thr | missense_variant | 7/16 | ENST00000450993.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCD4 | ENST00000450993.7 | c.883C>A | p.Pro295Thr | missense_variant | 7/16 | 1 | NM_032726.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249300Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135248
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461666Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727122
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74382
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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 | Feb 21, 2024 | The c.883C>A (p.P295T) alteration is located in exon 7 (coding exon 6) of the PLCD4 gene. This alteration results from a C to A substitution at nucleotide position 883, causing the proline (P) at amino acid position 295 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of catalytic residue at M292 (P = 0.0291);Gain of catalytic residue at M292 (P = 0.0291);Gain of catalytic residue at M292 (P = 0.0291);
MVP
MPC
ClinPred
D
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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