Variant 2-12723562-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000155926.9(TRIB2):c.563+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,611,946 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 10 hom., cov: 33)

Exomes 𝑓: 0.011 ( 102 hom. )

Consequence

TRIB2
ENST00000155926.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.87

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]

TRIB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-12723562-A-T is Benign according to our data. Variant chr2-12723562-A-T is described in ClinVar as [Benign]. Clinvar id is 774809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1338 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIB2	NM_021643.4 linkuse as main transcript	c.563+10A>T		intron_variant		ENST00000155926.9	NP_067675.1
TRIB2	NR_027303.2 linkuse as main transcript	n.368+10A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
TRIB2	ENST00000155926.9 linkuse as main transcript	c.563+10A>T	intron_variant	1	NM_021643.4	ENSP00000155926	P1
TRIB2	ENST00000381465.2 linkuse as main transcript	c.155+10A>T	intron_variant	2		ENSP00000370874
TRIB2	ENST00000405331.3 linkuse as main transcript	c.563+10A>T	intron_variant	2		ENSP00000384260

Frequencies

GnomAD3 genomes

AF:

0.00879

AC:

1338

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00975

AC:

2388

AN:

244968

Hom.:

AF XY:

0.00996

AC XY:

1328

AN XY:

133294

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.0232

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.00966

GnomAD4 exome

AF:

0.0111

AC:

16200

AN:

1459628

Hom.:

102

Cov.:

AF XY:

0.0111

AC XY:

8066

AN XY:

726030

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00335

Gnomad4 FIN exome

AF:

0.0211

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00945

GnomAD4 genome

AF:

0.00878

AC:

1338

AN:

152318

Hom.:

Cov.:

AF XY:

0.00917

AC XY:

683

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0223

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00615

Hom.:

Bravo

AF:

0.00729

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0030

DANN

Benign

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over