rs149772375

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_003184.4(TAF2):c.1655A>T(p.Tyr552Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00243 in 1,613,806 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 14 hom. )

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.27

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 -15 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=0.008978754).

BP6

Variant 8-119788818-T-A is Benign according to our data. Variant chr8-119788818-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 436940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF2	NM_003184.4 linkuse as main transcript	c.1655A>T	p.Tyr552Phe	missense_variant	13/26	ENST00000378164.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF2	ENST00000378164.7 linkuse as main transcript	c.1655A>T	p.Tyr552Phe	missense_variant	13/26	1	NM_003184.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00266

AC:

669

AN:

251358

Hom.:

AF XY:

0.00260

AC XY:

353

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00572

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00249

AC:

3634

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

1828

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00601

Gnomad4 ASJ exome

AF:

0.00742

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.00250

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00187

AC:

285

AN:

152268

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00237

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00259

AC:

314

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	TAF2: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 13, 2018

- -

Microcephaly-thin corpus callosum-intellectual disability syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.18

Eigen_PC

Benign

0.062

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.014

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.66

REVEL

Benign

0.15

Sift

Benign

0.67

Sift4G

Benign

0.68

Polyphen

0.0040

Vest4

0.67

MVP

0.33

MPC

0.37

ClinPred

0.026

GERP RS

5.6

Varity_R

0.33

gMVP

0.35

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