2-12718513-C-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_021643.4(TRIB2):c.206C>A(p.Pro69His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
TRIB2
NM_021643.4 missense
NM_021643.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 7.91
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIB2 | NM_021643.4 | c.206C>A | p.Pro69His | missense_variant | 1/3 | ENST00000155926.9 | |
TRIB2 | NR_027303.2 | n.75+1503C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIB2 | ENST00000155926.9 | c.206C>A | p.Pro69His | missense_variant | 1/3 | 1 | NM_021643.4 | P1 | |
TRIB2 | ENST00000405331.3 | c.206C>A | p.Pro69His | missense_variant | 1/3 | 2 | |||
TRIB2 | ENST00000381465.2 | c.-139+1503C>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152196Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727242
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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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 submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.206C>A (p.P69H) alteration is located in exon 1 (coding exon 1) of the TRIB2 gene. This alteration results from a C to A substitution at nucleotide position 206, causing the proline (P) at amino acid position 69 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP
MPC
ClinPred
D
GERP RS
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