GeneBe

rs2784075

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021138.4(TRAF2):​c.-28-239T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TRAF2
NM_021138.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

Publications

7 publications found
Variant links:
Genes affected
TRAF2 (HGNC:12032): (TNF receptor associated factor 2) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021138.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TRAF2
NM_021138.4
MANE Select
c.-28-239T>A
intron
N/ANP_066961.2

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TRAF2
ENST00000247668.7
TSL:1 MANE Select
c.-28-239T>A
intron
N/AENSP00000247668.2
TRAF2
ENST00000850853.1
c.-28-239T>A
intron
N/AENSP00000520942.1
TRAF2
ENST00000429509.5
TSL:3
c.-28-239T>A
intron
N/AENSP00000406524.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
439268
Hom.:
0
Cov.:
6
AF XY:
0.00
AC XY:
0
AN XY:
206262
African (AFR)
AF:
0.00
AC:
0
AN:
8124
American (AMR)
AF:
0.00
AC:
0
AN:
474
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2686
East Asian (EAS)
AF:
0.00
AC:
0
AN:
1892
South Asian (SAS)
AF:
0.00
AC:
0
AN:
8626
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
118
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
886
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
402068
Other (OTH)
AF:
0.00
AC:
0
AN:
14394
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.067
DANN
Benign
0.45
PhyloP100
-2.5
RBP_binding_hub_radar
0.67
RBP_regulation_power_radar
1.8

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

Other links and lift over

dbSNP: rs2784075; hg19: chr9-139792926; API