2-12718363-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021643.4(TRIB2):ā€‹c.56A>Gā€‹(p.Asn19Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

TRIB2
NM_021643.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11723256).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRIB2NM_021643.4 linkuse as main transcriptc.56A>G p.Asn19Ser missense_variant 1/3 ENST00000155926.9
TRIB2NR_027303.2 linkuse as main transcriptn.75+1353A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIB2ENST00000155926.9 linkuse as main transcriptc.56A>G p.Asn19Ser missense_variant 1/31 NM_021643.4 P1
TRIB2ENST00000405331.3 linkuse as main transcriptc.56A>G p.Asn19Ser missense_variant 1/32
TRIB2ENST00000381465.2 linkuse as main transcriptc.-139+1353A>G intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000113

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 GeneticsJul 11, 2022The c.56A>G (p.N19S) alteration is located in exon 1 (coding exon 1) of the TRIB2 gene. This alteration results from a A to G substitution at nucleotide position 56, causing the asparagine (N) at amino acid position 19 to be replaced by a serine (S). 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
0.070
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.071
T;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.029
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.86
D;D
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.
MutationTaster
Benign
0.67
D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.16
N;N
REVEL
Benign
0.064
Sift
Benign
0.40
T;T
Sift4G
Benign
0.46
T;T
Polyphen
0.0
B;.
Vest4
0.085
MutPred
0.22
Gain of phosphorylation at N19 (P = 0.0186);Gain of phosphorylation at N19 (P = 0.0186);
MVP
0.30
MPC
0.66
ClinPred
0.75
D
GERP RS
4.2
Varity_R
0.15
gMVP
0.31

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: rs1395559730; hg19: chr2-12858489; API