chr2-218622719-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_032726.4(PLCD4):c.613C>T(p.Arg205Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,614,008 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 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
PLCD4
NM_032726.4 missense
NM_032726.4 missense
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 2.24
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.751
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCD4 | NM_032726.4 | c.613C>T | p.Arg205Cys | missense_variant | 6/16 | ENST00000450993.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCD4 | ENST00000450993.7 | c.613C>T | p.Arg205Cys | missense_variant | 6/16 | 1 | NM_032726.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 249282Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135236
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GnomAD4 exome AF: 0.000128 AC: 187AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.000125 AC XY: 91AN XY: 727136
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74458
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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 | Nov 07, 2022 | The c.613C>T (p.R205C) alteration is located in exon 6 (coding exon 5) of the PLCD4 gene. This alteration results from a C to T substitution at nucleotide position 613, causing the arginine (R) at amino acid position 205 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of methylation at K204 (P = 0.0172);Gain of methylation at K204 (P = 0.0172);Gain of methylation at K204 (P = 0.0172);
MVP
MPC
ClinPred
D
GERP RS
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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