chr2-12718542-G-C

Position:

• chr2-12718542-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76

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]

ACMG classification

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
TRIB2	NM_021643.4	c.235G>C	p.Val79Leu	missense_variant	1/3	ENST00000155926.9
TRIB2	NR_027303.2	n.75+1532G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB2	ENST00000155926.9	c.235G>C	p.Val79Leu	missense_variant	1/3	1	NM_021643.4	P1
TRIB2	ENST00000405331.3	c.235G>C	p.Val79Leu	missense_variant	1/3	2
TRIB2	ENST00000381465.2	c.-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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The 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;