chr2-218622824-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032726.4(PLCD4):​c.718T>C​(p.Cys240Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PLCD4
NM_032726.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.219
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]

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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=0.08907467).
BP6
Variant 2-218622824-T-C is Benign according to our data. Variant chr2-218622824-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2494675.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLCD4NM_032726.4 linkuse as main transcriptc.718T>C p.Cys240Arg missense_variant 6/16 ENST00000450993.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLCD4ENST00000450993.7 linkuse as main transcriptc.718T>C p.Cys240Arg missense_variant 6/161 NM_032726.4 P1Q9BRC7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 06, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.055
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
1.1
DANN
Benign
0.66
DEOGEN2
Benign
0.090
T;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.47
T;.;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.089
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.55
N;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.12
N;N;N
REVEL
Benign
0.060
Sift
Benign
0.18
T;T;T
Sift4G
Benign
0.39
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.10
MutPred
0.65
Gain of disorder (P = 0.0129);Gain of disorder (P = 0.0129);Gain of disorder (P = 0.0129);
MVP
0.15
MPC
0.38
ClinPred
0.041
T
GERP RS
1.9
Varity_R
0.059
gMVP
0.35

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: rs1695946733; hg19: chr2-219487547; API