6-149370155-AT-A

Variant names:

• chr6-149370155-AT-A
• rs35974009
• NM_001292034.3:c.102+58delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001292034.3(TAB2):​c.102+58delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,441,954 control chromosomes in the GnomAD database, including 16,450 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1743 hom., cov: 30)
  • Exomes 𝑓: 0.13 (14707 hom.)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0220
• Publications: 2 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 -10 ACMG points.

• BP6: Variant 6-149370155-AT-A is Benign according to our data. Variant chr6-149370155-AT-A is described in ClinVar as [Benign]. Clinvar id is 1235661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.102+58delT		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+57delT		intron_variant	Intron 2 of 6	1	NM_001292034.3	ENSP00000490618.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18593 AN: 152068 Hom.: 1739 Cov.: 30

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.126 AC: 161915 AN: 1289768 Hom.: 14707 AF XY: 0.127 AC XY: 82522 AN XY: 649920

African (AFR) AF: 0.0569 AC: 1716 AN: 30150

American (AMR) AF: 0.310 AC: 13449 AN: 43334

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2975 AN: 24920

East Asian (EAS) AF: 0.489 AC: 18934 AN: 38708

South Asian (SAS) AF: 0.204 AC: 16694 AN: 81942

European-Finnish (FIN) AF: 0.119 AC: 6123 AN: 51424

Middle Eastern (MID) AF: 0.124 AC: 655 AN: 5268

European-Non Finnish (NFE) AF: 0.0976 AC: 93660 AN: 959294

Other (OTH) AF: 0.141 AC: 7709 AN: 54728

GnomAD4 genome AF: 0.122 AC: 18606 AN: 152186 Hom.: 1743 Cov.: 30 AF XY: 0.128 AC XY: 9551 AN XY: 74418

African (AFR) AF: 0.0617 AC: 2564 AN: 41532

American (AMR) AF: 0.211 AC: 3226 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2656 AN: 5170

South Asian (SAS) AF: 0.211 AC: 1019 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1287 AN: 10592

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7114 AN: 67984

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.115 Hom.: 157

Bravo AF: 0.130

Asia WGS AF: 0.331 AC: 1147 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.022
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: rs35974009; hg19: chr6-149691291;