chr8-119732109-T-C

Position:

chr8-119732109-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The ENST00000378164.7(TAF2):c.3415A>G(p.Thr1139Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,613,892 control chromosomes in the GnomAD database, including 11,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 4033 hom., cov: 32)

Exomes 𝑓: 0.081 ( 7664 hom. )

Consequence

TAF2
ENST00000378164.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.536

Variant links:

Genes affected

TAF2 (HGNC:11536): (TATA-box binding protein associated factor 2) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators. [provided by RefSeq, Jul 2008]

TAF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TAF2. . Gene score misZ 2.7836 (greater than the threshold 3.09). Trascript score misZ 3.5113 (greater than threshold 3.09). GenCC has associacion of gene with microcephaly-thin corpus callosum-intellectual disability syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=6.3571334E-4).

BP6

Variant 8-119732109-T-C is Benign according to our data. Variant chr8-119732109-T-C is described in ClinVar as [Benign]. Clinvar id is 1170265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4 linkuse as main transcript	c.3415A>G	p.Thr1139Ala	missense_variant	26/26	ENST00000378164.7	NP_003175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF2	ENST00000378164.7 linkuse as main transcript	c.3415A>G	p.Thr1139Ala	missense_variant	26/26	1	NM_003184.4	ENSP00000367406	P1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25237

AN:

152056

Hom.:

4022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0702

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.00732

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0763

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0686

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.0943

AC:

23685

AN:

251174

Hom.:

2298

AF XY:

0.0913

AC XY:

12397

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.0546

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.00490

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.0753

Gnomad NFE exome

AF:

0.0669

Gnomad OTH exome

AF:

0.0712

GnomAD4 exome

AF:

0.0812

AC:

118658

AN:

1461718

Hom.:

7664

Cov.:

AF XY:

0.0819

AC XY:

59561

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.0566

Gnomad4 ASJ exome

AF:

0.0548

Gnomad4 EAS exome

AF:

0.00267

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.0745

Gnomad4 NFE exome

AF:

0.0699

Gnomad4 OTH exome

AF:

0.0930

GnomAD4 genome

AF:

0.166

AC:

25284

AN:

152174

Hom.:

4033

Cov.:

AF XY:

0.162

AC XY:

12043

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.421

Gnomad4 AMR

AF:

0.0703

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.00733

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.0763

Gnomad4 NFE

AF:

0.0686

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0830

Hom.:

2368

Bravo

AF:

0.173

TwinsUK

AF:

0.0731

AC:

271

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.419

AC:

1847

ESP6500EA

AF:

0.0673

AC:

579

ExAC

AF:

0.103

AC:

12525

Asia WGS

AF:

0.0910

AC:

317

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0599

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -

TAF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.055

DANN

Benign

0.59

DEOGEN2

Benign

0.0074

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

0.00064

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.051

Sift

Benign

0.46

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0

B;.

Vest4

0.014

MPC

0.40

ClinPred

0.013

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.067

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over