rs532367

Variant names:

• chr6-149221662-A-G
• rs532367
• NM_001292035.3:c.6+2886A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292035.3(TAB2):​c.6+2886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,934 control chromosomes in the GnomAD database, including 27,354 homozygotes. 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: 𝑓 0.59 (27354 hom., cov: 31)
• Consequence: TAB2 NM_001292035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 5 publications found

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

ENSG00000228408 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292035.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	NM_001292035.3		c.6+2886A>G		intron	N/A	NP_001278964.1	B4DIR9
	TAB2	NR_125861.2		n.313+2886A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000606202.1	TSL:4	c.-121+2886A>G		intron	N/A	ENSP00000476139.1	U3KQR0
	ENSG00000228408	ENST00000443992.1	TSL:2	n.238+2886A>G		intron	N/A
	ENSG00000228408	ENST00000445901.1	TSL:2	n.79+2886A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89890 AN: 151814 Hom.: 27320 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.586

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 89975 AN: 151934 Hom.: 27354 Cov.: 31 AF XY: 0.589 AC XY: 43732 AN XY: 74256

African (AFR) AF: 0.740 AC: 30650 AN: 41440

American (AMR) AF: 0.589 AC: 8990 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3466

East Asian (EAS) AF: 0.482 AC: 2486 AN: 5156

South Asian (SAS) AF: 0.573 AC: 2750 AN: 4802

European-Finnish (FIN) AF: 0.486 AC: 5135 AN: 10556

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36297 AN: 67948

Other (OTH) AF: 0.588 AC: 1237 AN: 2102

Alfa AF: 0.583 Hom.: 3422

Bravo AF: 0.606

Asia WGS AF: 0.559 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs532367; hg19: chr6-149542798; COSMIC: COSV71379995;