8-119791397-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003184.4(TAF2):c.1340G>A(p.Ser447Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S447T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11212647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.1340G>A	p.Ser447Asn	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>A	p.Ser447Asn	missense_variant	Exon 11 of 26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.1340G>A	p.Ser447Asn	missense_variant	Exon 11 of 27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.1340G>A	p.Ser447Asn	missense_variant	Exon 11 of 26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.1340G>A	p.Ser447Asn	missense_variant	Exon 11 of 25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.1226G>A	p.Ser409Asn	missense_variant	Exon 10 of 25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144.1 link	c.1340G>A	p.Ser447Asn	missense_variant	Exon 11 of 26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.1340G>A		non_coding_transcript_exon_variant	Exon 11 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*732G>A		non_coding_transcript_exon_variant	Exon 11 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*1212G>A		non_coding_transcript_exon_variant	Exon 13 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*2807G>A		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*1041G>A		non_coding_transcript_exon_variant	Exon 9 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*1058G>A		non_coding_transcript_exon_variant	Exon 12 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*1155G>A		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.1254G>A		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*759G>A		non_coding_transcript_exon_variant	Exon 8 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689164.1 link	n.1140G>A		non_coding_transcript_exon_variant	Exon 9 of 24			ENSP00000508729.1	A0A8I5KR26
TAF2	ENST00000689919.1 link	n.*1058G>A		non_coding_transcript_exon_variant	Exon 12 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*576G>A		non_coding_transcript_exon_variant	Exon 11 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.1340G>A		non_coding_transcript_exon_variant	Exon 11 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691847.1 link	n.*641G>A		non_coding_transcript_exon_variant	Exon 10 of 24			ENSP00000509663.1	A0A8I5QJJ6
TAF2	ENST00000691880.1 link	n.*996G>A		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*1041G>A		non_coding_transcript_exon_variant	Exon 9 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*1208G>A		non_coding_transcript_exon_variant	Exon 13 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*727G>A		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685503.1 link	n.*732G>A		3_prime_UTR_variant	Exon 11 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*1212G>A		3_prime_UTR_variant	Exon 13 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*2807G>A		3_prime_UTR_variant	Exon 10 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*1041G>A		3_prime_UTR_variant	Exon 9 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*1058G>A		3_prime_UTR_variant	Exon 12 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*1155G>A		3_prime_UTR_variant	Exon 10 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000688037.1 link	n.*759G>A		3_prime_UTR_variant	Exon 8 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*1058G>A		3_prime_UTR_variant	Exon 12 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*576G>A		3_prime_UTR_variant	Exon 11 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000691847.1 link	n.*641G>A		3_prime_UTR_variant	Exon 10 of 24			ENSP00000509663.1	A0A8I5QJJ6
TAF2	ENST00000691880.1 link	n.*996G>A		3_prime_UTR_variant	Exon 10 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*1041G>A		3_prime_UTR_variant	Exon 9 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*1208G>A		3_prime_UTR_variant	Exon 13 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*727G>A		3_prime_UTR_variant	Exon 10 of 25			ENSP00000509603.1	A0A8I5QJI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250970

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461456

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.0000224

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111784

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.57

M_CAP

Benign

0.0070

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

4.8

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.20

REVEL

Benign

0.088

Sift

Benign

0.13

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.077

MutPred

0.68

Loss of catalytic residue at S447 (P = 0.1688);

MVP

0.13

MPC

0.38

ClinPred

0.23

GERP RS

3.0

Varity_R

0.053

gMVP

0.53

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over