2-12718542-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021643.4(TRIB2):​c.235G>C​(p.Val79Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TRIB2
NM_021643.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76
Variant links:
Genes affected
TRIB2 (HGNC:30809): (tribbles pseudokinase 2) This gene encodes one of three members of the Tribbles family. The Tribbles members share a Trb domain, which is homologous to protein serine-threonine kinases, but lacks the active site lysine and probably lacks a catalytic function. The Tribbles proteins interact and modulate the activity of signal transduction pathways in a number of physiological and pathological processes. This Tribbles member induces apoptosis of cells mainly of the hematopoietic origin. It has been identified as a protein up-regulated by inflammatory stimuli in myeloid (THP-1) cells, and also as an oncogene that inactivates the transcription factor C/EBPalpha (CCAAT/enhancer-binding protein alpha) and causes acute myelogenous leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13926512).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRIB2NM_021643.4 linkuse as main transcriptc.235G>C p.Val79Leu missense_variant 1/3 ENST00000155926.9
TRIB2NR_027303.2 linkuse as main transcriptn.75+1532G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIB2ENST00000155926.9 linkuse as main transcriptc.235G>C p.Val79Leu missense_variant 1/31 NM_021643.4 P1
TRIB2ENST00000405331.3 linkuse as main transcriptc.235G>C p.Val79Leu missense_variant 1/32
TRIB2ENST00000381465.2 linkuse as main transcriptc.-139+1532G>C intron_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsNov 08, 2022The c.235G>C (p.V79L) alteration is located in exon 1 (coding exon 1) of the TRIB2 gene. This alteration results from a G to C substitution at nucleotide position 235, causing the valine (V) at amino acid position 79 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
0.075
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.85
T;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.1
L;.
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.44
N;N
REVEL
Benign
0.056
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;.
Vest4
0.13
MutPred
0.31
Gain of catalytic residue at V79 (P = 0.1258);Gain of catalytic residue at V79 (P = 0.1258);
MVP
0.48
MPC
0.84
ClinPred
0.77
D
GERP RS
5.2
Varity_R
0.077
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-12858668; API