rs755760670

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003184.4(TAF2):c.3578G>A(p.Arg1193His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.80

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08079541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.3578G>A	p.Arg1193His	missense_variant	Exon 26 of 26	ENST00000378164.7	NP_003175.2	Q6P1X5B3KMD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAF2	ENST00000378164.7 link	c.3578G>A	p.Arg1193His	missense_variant	Exon 26 of 26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.3734G>A	p.Arg1245His	missense_variant	Exon 27 of 27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.3623G>A	p.Arg1208His	missense_variant	Exon 26 of 26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.3467G>A	p.Arg1156His	missense_variant	Exon 25 of 25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.3464G>A	p.Arg1155His	missense_variant	Exon 25 of 25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144 link	c.*709G>A		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.*1103G>A		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2970G>A		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3450G>A		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*5045G>A		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3279G>A		non_coding_transcript_exon_variant	Exon 24 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3296G>A		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3393G>A		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2223G>A		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2997G>A		non_coding_transcript_exon_variant	Exon 23 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3185G>A		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2814G>A		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1990G>A		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3234G>A		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3444G>A		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3446G>A		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2965G>A		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685202.1 link	n.*1103G>A		3_prime_UTR_variant	Exon 27 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2970G>A		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3450G>A		3_prime_UTR_variant	Exon 28 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*5045G>A		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3279G>A		3_prime_UTR_variant	Exon 24 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3296G>A		3_prime_UTR_variant	Exon 27 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3393G>A		3_prime_UTR_variant	Exon 25 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2223G>A		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2997G>A		3_prime_UTR_variant	Exon 23 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3185G>A		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2814G>A		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1990G>A		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3234G>A		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3444G>A		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3446G>A		3_prime_UTR_variant	Exon 28 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2965G>A		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000689164.1 link	n.*4196G>A		downstream_gene_variant				ENSP00000508729.1	A0A8I5KR26

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251180

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000177

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3578G>A (p.R1193H) alteration is located in exon 26 (coding exon 26) of the TAF2 gene. This alteration results from a G to A substitution at nucleotide position 3578, causing the arginine (R) at amino acid position 1193 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Aug 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2508650). This variant has not been reported in the literature in individuals affected with TAF2-related conditions. This variant is present in population databases (rs755760670, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1193 of the TAF2 protein (p.Arg1193His). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.073

Sift

Benign

0.038

D;D

Sift4G

Benign

0.27

T;D

Polyphen

0.0070

B;.

Vest4

0.24

MVP

0.36

MPC

0.81

ClinPred

0.54

GERP RS

4.1

Varity_R

0.044

gMVP

0.12

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