Genetic Variant TAB2:c.102+17T>A (chr6-149370116-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001292034.3(TAB2):c.102+17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,836 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TAB2
NM_001292034.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210

Publications

0 publications found

Variant links:

Genes affected

TAB2 (HGNC:17075): (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, and it thus serves as an adaptor that links MAP3K7 and TRAF6. This protein, along with TAB1 and MAP3K7, also participates in the signal transduction induced by TNFSF11/RANKl through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Studies of the related mouse protein indicate that it functions to protect against liver damage caused by chemical stressors. Mutations in this gene cause congenital heart defects, multiple types, 2 (CHTD2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

TAB2 Gene-Disease associations (from GenCC):

chromosome 6q24-q25 deletion syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
congenital heart defects, multiple types, 2
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
polyvalvular heart disease syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TAB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TAB2	NM_001292034.3	MANE Select	c.102+17T>A	intron	N/A	NP_001278963.1	Q9NYJ8-1
TAB2	NM_001369506.1		c.102+17T>A	intron	N/A	NP_001356435.1	Q9NYJ8-1
TAB2	NM_015093.6		c.102+17T>A	intron	N/A	NP_055908.1	Q9NYJ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TAB2	ENST00000637181.2	TSL:1 MANE Select	c.102+17T>A	intron	N/A	ENSP00000490618.1	Q9NYJ8-1
TAB2	ENST00000470466.5	TSL:1	n.102+17T>A	intron	N/A	ENSP00000432709.1	Q9NYJ8-2
TAB2	ENST00000367456.5	TSL:5	c.102+17T>A	intron	N/A	ENSP00000356426.1	Q9NYJ8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452836

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723320

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33308

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

86076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103962

Other (OTH)

AF:

0.0000166

AC:

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.021

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over