chr8-119732046-T-G

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.3478A>C(p.Lys1160Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 6.29

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=0.23793513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.3478A>C	p.Lys1160Gln	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.3478A>C	p.Lys1160Gln	missense_variant	Exon 26 of 26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.3634A>C	p.Lys1212Gln	missense_variant	Exon 27 of 27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.3523A>C	p.Lys1175Gln	missense_variant	Exon 26 of 26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.3367A>C	p.Lys1123Gln	missense_variant	Exon 25 of 25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.3364A>C	p.Lys1122Gln	missense_variant	Exon 25 of 25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144 link	c.*609A>C		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.*1003A>C		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2870A>C		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3350A>C		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*4945A>C		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3179A>C		non_coding_transcript_exon_variant	Exon 24 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3196A>C		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3293A>C		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2123A>C		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2897A>C		non_coding_transcript_exon_variant	Exon 23 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3085A>C		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2714A>C		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1890A>C		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3134A>C		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3344A>C		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3346A>C		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2865A>C		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685202.1 link	n.*1003A>C		3_prime_UTR_variant	Exon 27 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2870A>C		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3350A>C		3_prime_UTR_variant	Exon 28 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*4945A>C		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3179A>C		3_prime_UTR_variant	Exon 24 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3196A>C		3_prime_UTR_variant	Exon 27 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3293A>C		3_prime_UTR_variant	Exon 25 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2123A>C		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2897A>C		3_prime_UTR_variant	Exon 23 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3085A>C		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2714A>C		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1890A>C		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3134A>C		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3344A>C		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3346A>C		3_prime_UTR_variant	Exon 28 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2865A>C		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000689164.1 link	n.*4096A>C		downstream_gene_variant				ENSP00000508729.1	A0A8I5KR26

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251348

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Uncertain:1

Mar 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3478A>C (p.K1160Q) alteration is located in exon 26 (coding exon 26) of the TAF2 gene. This alteration results from a A to C substitution at nucleotide position 3478, causing the lysine (K) at amino acid position 1160 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Nov 26, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ClinVar contains an entry for this variant (Variation ID: 436939). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with TAF2-related conditions. This variant is present in population databases (rs755785500, gnomAD 0.03%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1160 of the TAF2 protein (p.Lys1160Gln). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.058

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.97

L;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.012

D;T

Polyphen

0.98

D;.

Vest4

0.40

MutPred

0.25

Loss of methylation at K1160 (P = 0.0047);.;

MVP

0.39

MPC

1.3

ClinPred

0.53

GERP RS

6.0

Varity_R

0.69

gMVP

0.23

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