rs6570963

Variant names:

• chr6-149370219-T-G
• rs6570963
• NM_001292034.3:c.102+120T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001292034.3(TAB2):​c.102+120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 933,332 control chromosomes in the GnomAD database, including 110,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15182 hom., cov: 32)
  • Exomes 𝑓: 0.49 (95013 hom.)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.264
• Publications: 11 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-149370219-T-G is Benign according to our data. Variant chr6-149370219-T-G is described in ClinVar as [Benign]. Clinvar id is 1259650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.102+120T>G		intron_variant	Intron 2 of 6	ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2	c.102+120T>G		intron_variant	Intron 2 of 6	1	NM_001292034.3	ENSP00000490618.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66430 AN: 151944 Hom.: 15187 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.488 AC: 380895 AN: 781270 Hom.: 95013 AF XY: 0.487 AC XY: 198513 AN XY: 407962

African (AFR) AF: 0.309 AC: 6078 AN: 19650

American (AMR) AF: 0.394 AC: 13689 AN: 34748

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 11073 AN: 21418

East Asian (EAS) AF: 0.302 AC: 9986 AN: 33038

South Asian (SAS) AF: 0.425 AC: 28319 AN: 66664

European-Finnish (FIN) AF: 0.464 AC: 16873 AN: 36370

Middle Eastern (MID) AF: 0.539 AC: 1591 AN: 2954

European-Non Finnish (NFE) AF: 0.521 AC: 275167 AN: 528380

Other (OTH) AF: 0.476 AC: 18119 AN: 38048

GnomAD4 genome AF: 0.437 AC: 66446 AN: 152062 Hom.: 15182 Cov.: 32 AF XY: 0.433 AC XY: 32220 AN XY: 74346

African (AFR) AF: 0.314 AC: 13027 AN: 41484

American (AMR) AF: 0.438 AC: 6693 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1838 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5178

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4899 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34878 AN: 67954

Other (OTH) AF: 0.447 AC: 941 AN: 2106

Alfa AF: 0.489 Hom.: 75153

Bravo AF: 0.427

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6570963; hg19: chr6-149691355; COSMIC: COSV53854993;