rs774247595
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002663.5(PLD2):c.2447G>A(p.Arg816Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000813 in 1,611,734 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 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 0 hom. )
Consequence
PLD2
NM_002663.5 missense
NM_002663.5 missense
Scores
8
8
3
Clinical Significance
Conservation
PhyloP100: 8.11
Genes affected
PLD2 (HGNC:9068): (phospholipase D2) The protein encoded by this gene catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline. The activity of the encoded enzyme is enhanced by phosphatidylinositol 4,5-bisphosphate and ADP-ribosylation factor-1. This protein localizes to the peripheral membrane and may be involved in cytoskeletal organization, cell cycle control, transcriptional regulation, and/or regulated secretion. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]
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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, 0.886
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLD2 | NM_002663.5 | c.2447G>A | p.Arg816Gln | missense_variant | 23/25 | ENST00000263088.11 | |
PLD2 | XM_047436300.1 | c.2087G>A | p.Arg696Gln | missense_variant | 21/23 | ||
PLD2 | NM_001243108.2 | c.2429+18G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLD2 | ENST00000263088.11 | c.2447G>A | p.Arg816Gln | missense_variant | 23/25 | 1 | NM_002663.5 | P1 | |
PLD2 | ENST00000572940.5 | c.2429+18G>A | intron_variant | 1 | |||||
PLD2 | ENST00000576864.1 | c.341G>A | p.Arg114Gln | missense_variant | 4/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000644 AC: 16AN: 248586Hom.: 0 AF XY: 0.0000893 AC XY: 12AN XY: 134344
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GnomAD4 exome AF: 0.0000836 AC: 122AN: 1459576Hom.: 0 Cov.: 33 AF XY: 0.0000868 AC XY: 63AN XY: 725840
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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