chr8-119791397-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

microcephaly-thin corpus callosum-intellectual disability syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

TAF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1165134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAF2	NM_003184.4	MANE Select	c.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	NP_003175.2
TAF2	NM_001437338.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 27	NP_001424267.1
TAF2	NM_001438084.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	NP_001425013.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAF2	ENST00000378164.7	TSL:1 MANE Select	c.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	ENSP00000367406.2
TAF2	ENST00000686879.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 27	ENSP00000509206.1
TAF2	ENST00000685235.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	ENSP00000510174.1

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

GnomAD2 exomes

AF:

0.684

AC:

171765

AN:

250970

AF XY:

0.684

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 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

African (AFR)

AF:

0.767

AC:

25660

AN:

33436

American (AMR)

AF:

0.691

AC:

30893

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

19653

AN:

26110

East Asian (EAS)

AF:

0.448

AC:

17737

AN:

39616

South Asian (SAS)

AF:

0.667

AC:

57537

AN:

86222

European-Finnish (FIN)

AF:

0.690

AC:

36810

AN:

53346

Middle Eastern (MID)

AF:

0.811

AC:

4669

AN:

5758

European-Non Finnish (NFE)

AF:

0.695

AC:

772843

AN:

1111464

Other (OTH)

AF:

0.698

AC:

42076

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15126

30252

45377

60503

75629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19556

39112

58668

78224

97780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.711

AC:

108036

AN:

151968

Hom.:

38559

Cov.:

AF XY:

0.709

AC XY:

52659

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.759

AC:

31460

AN:

41440

American (AMR)

AF:

0.727

AC:

11100

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

2606

AN:

3472

East Asian (EAS)

AF:

0.462

AC:

2384

AN:

5160

South Asian (SAS)

AF:

0.659

AC:

3174

AN:

4820

European-Finnish (FIN)

AF:

0.689

AC:

7243

AN:

10518

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47589

AN:

67962

Other (OTH)

AF:

0.735

AC:

1553

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1629

3258

4886

6515

8144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

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

PhyloP100

4.8

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over