8-119732159-C-T

Position:

chr8-119732159-C-T

Variant summary

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

The ENST00000378164.7(TAF2):c.3365G>A(p.Ser1122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,613,680 control chromosomes in the GnomAD database, including 5,010 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 0.098 ( 1089 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3921 hom. )

Consequence

TAF2
ENST00000378164.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.19

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=8.4427E-4).

BP6

Variant 8-119732159-C-T is Benign according to our data. Variant chr8-119732159-C-T is described in ClinVar as [Benign]. Clinvar id is 1170266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 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.3365G>A	p.Ser1122Asn	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.3365G>A	p.Ser1122Asn	missense_variant	26/26	1	NM_003184.4	ENSP00000367406	P1

Frequencies

GnomAD3 genomes

AF:

0.0976

AC:

14838

AN:

152078

Hom.:

1089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.0758

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0803

GnomAD3 exomes

AF:

0.0619

AC:

15569

AN:

251316

Hom.:

797

AF XY:

0.0590

AC XY:

8007

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.0409

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0410

Gnomad FIN exome

AF:

0.0751

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0498

GnomAD4 exome

AF:

0.0661

AC:

96625

AN:

1461484

Hom.:

3921

Cov.:

AF XY:

0.0650

AC XY:

47251

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0414

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.0677

Gnomad4 OTH exome

AF:

0.0664

GnomAD4 genome

AF:

0.0976

AC:

14850

AN:

152196

Hom.:

1089

Cov.:

AF XY:

0.0943

AC XY:

7021

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0404

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.0758

Gnomad4 NFE

AF:

0.0664

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0623

Hom.:

983

Bravo

AF:

0.0989

TwinsUK

AF:

0.0701

AC:

260

ALSPAC

AF:

0.0664

AC:

256

ESP6500AA

AF:

0.208

AC:

918

ESP6500EA

AF:

0.0629

AC:

541

ExAC

AF:

0.0659

AC:

7996

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0564

EpiControl

AF:

0.0560

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 25, 2024	- -

TAF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 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

0.073

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0093

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.00084

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.057

Sift

Benign

0.51

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;.

Vest4

0.0050

MPC

0.38

ClinPred

0.00053

GERP RS

3.2

Varity_R

0.034

gMVP

0.066

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