chr8-119791397-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003184.4(TAF2):c.1340G>C(p.Ser447Thr) variant causes a missense change. The variant allele was found at a frequency of 0.692 in 1,612,938 control chromosomes in the GnomAD database, including 388,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.71 ( 38559 hom., cov: 32)

Exomes 𝑓: 0.69 ( 349458 hom. )

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.80

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.565472E-7).

BP6

Variant 8-119791397-C-G is Benign according to our data. Variant chr8-119791397-C-G is described in ClinVar as [Benign]. Clinvar id is 1165134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-119791397-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.1340G>C	p.Ser447Thr	missense_variant	Exon 11 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.1340G>C	p.Ser447Thr	missense_variant	Exon 11 of 26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.1340G>C	p.Ser447Thr	missense_variant	Exon 11 of 27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.1340G>C	p.Ser447Thr	missense_variant	Exon 11 of 26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.1340G>C	p.Ser447Thr	missense_variant	Exon 11 of 25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.1226G>C	p.Ser409Thr	missense_variant	Exon 10 of 25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144.1 link	c.1340G>C	p.Ser447Thr	missense_variant	Exon 11 of 26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.1340G>C		non_coding_transcript_exon_variant	Exon 11 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*732G>C		non_coding_transcript_exon_variant	Exon 11 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*1212G>C		non_coding_transcript_exon_variant	Exon 13 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*2807G>C		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*1041G>C		non_coding_transcript_exon_variant	Exon 9 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*1058G>C		non_coding_transcript_exon_variant	Exon 12 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*1155G>C		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.1254G>C		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*759G>C		non_coding_transcript_exon_variant	Exon 8 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689164.1 link	n.1140G>C		non_coding_transcript_exon_variant	Exon 9 of 24			ENSP00000508729.1	A0A8I5KR26
TAF2	ENST00000689919.1 link	n.*1058G>C		non_coding_transcript_exon_variant	Exon 12 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*576G>C		non_coding_transcript_exon_variant	Exon 11 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.1340G>C		non_coding_transcript_exon_variant	Exon 11 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691847.1 link	n.*641G>C		non_coding_transcript_exon_variant	Exon 10 of 24			ENSP00000509663.1	A0A8I5QJJ6
TAF2	ENST00000691880.1 link	n.*996G>C		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*1041G>C		non_coding_transcript_exon_variant	Exon 9 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*1208G>C		non_coding_transcript_exon_variant	Exon 13 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*727G>C		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685503.1 link	n.*732G>C		3_prime_UTR_variant	Exon 11 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*1212G>C		3_prime_UTR_variant	Exon 13 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*2807G>C		3_prime_UTR_variant	Exon 10 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*1041G>C		3_prime_UTR_variant	Exon 9 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*1058G>C		3_prime_UTR_variant	Exon 12 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*1155G>C		3_prime_UTR_variant	Exon 10 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000688037.1 link	n.*759G>C		3_prime_UTR_variant	Exon 8 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*1058G>C		3_prime_UTR_variant	Exon 12 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*576G>C		3_prime_UTR_variant	Exon 11 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000691847.1 link	n.*641G>C		3_prime_UTR_variant	Exon 10 of 24			ENSP00000509663.1	A0A8I5QJJ6
TAF2	ENST00000691880.1 link	n.*996G>C		3_prime_UTR_variant	Exon 10 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*1041G>C		3_prime_UTR_variant	Exon 9 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*1208G>C		3_prime_UTR_variant	Exon 13 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*727G>C		3_prime_UTR_variant	Exon 10 of 25			ENSP00000509603.1	A0A8I5QJI9

Frequencies

GnomAD3 genomes

AF:

0.711

AC:

107949

AN:

151850

Hom.:

38530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.726

Gnomad ASJ

AF:

0.751

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.741

GnomAD3 exomes

AF:

0.684

AC:

171765

AN:

250970

Hom.:

59532

AF XY:

0.684

AC XY:

92723

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.760

Gnomad AMR exome

AF:

0.685

Gnomad ASJ exome

AF:

0.754

Gnomad EAS exome

AF:

0.462

Gnomad SAS exome

AF:

0.669

Gnomad FIN exome

AF:

0.694

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.702

GnomAD4 exome

AF:

0.690

AC:

1007878

AN:

1460970

Hom.:

349458

Cov.:

AF XY:

0.689

AC XY:

501054

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.767

Gnomad4 AMR exome

AF:

0.691

Gnomad4 ASJ exome

AF:

0.753

Gnomad4 EAS exome

AF:

0.448

Gnomad4 SAS exome

AF:

0.667

Gnomad4 FIN exome

AF:

0.690

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.711

AC:

108036

AN:

151968

Hom.:

38559

Cov.:

AF XY:

0.709

AC XY:

52659

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.727

Gnomad4 ASJ

AF:

0.751

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.659

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.700

Gnomad4 OTH

AF:

0.735

Alfa

AF:

0.692

Hom.:

25511

Bravo

AF:

0.715

TwinsUK

AF:

0.704

AC:

2611

ALSPAC

AF:

0.682

AC:

2629

ESP6500AA

AF:

0.769

AC:

3388

ESP6500EA

AF:

0.698

AC:

6004

ExAC

AF:

0.685

AC:

83114

Asia WGS

AF:

0.543

AC:

1886

AN:

3476

EpiCase

AF:

0.704

EpiControl

AF:

0.718

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly-thin corpus callosum-intellectual disability syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.013

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.23

MetaRNN

Benign

9.6e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.27

REVEL

Benign

0.087

Sift

Benign

0.64

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.043

MPC

0.37

ClinPred

0.0055

GERP RS

3.0

Varity_R

0.073

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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