16-66940222-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001365405.1(CES2):​c.424G>T​(p.Val142Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

CES2
NM_001365405.1 missense, splice_region

Scores

10
7
1
Splicing: ADA: 0.9992
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.67
Variant links:
Genes affected
CES2 (HGNC:1864): (carboxylesterase 2) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

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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, 0.902

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CES2NM_001365405.1 linkc.424G>T p.Val142Leu missense_variant, splice_region_variant Exon 4 of 12 ENST00000317091.10 NP_001352334.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CES2ENST00000317091.10 linkc.424G>T p.Val142Leu missense_variant, splice_region_variant Exon 4 of 12 1 NM_001365405.1 ENSP00000317842.5 O00748-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;T;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.90
D;D;D
MetaSVM
Pathogenic
0.91
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.9
D;.;D
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D;.;D
Sift4G
Uncertain
0.0020
D;.;D
Vest4
0.66
MVP
0.61
MPC
0.70
ClinPred
1.0
D
GERP RS
4.4

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.97
SpliceAI score (max)
0.030
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: rs72547532; hg19: chr16-66974125; API