8-119803881-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003184.4(TAF2):c.557C>G(p.Thr186Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 9.95

Publications

2 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 5 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.557C>G	p.Thr186Arg	missense_variant	Exon 5 of 26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 5 of 27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 5 of 26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 5 of 25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 5 of 25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144.1 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 5 of 26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000521007.2 link	c.557C>G	p.Thr186Arg	missense_variant	Exon 6 of 7	3		ENSP00000428484.2	E5RI28
TAF2	ENST00000685202.1 link	n.557C>G		non_coding_transcript_exon_variant	Exon 5 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.557C>G		non_coding_transcript_exon_variant	Exon 5 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*429C>G		non_coding_transcript_exon_variant	Exon 7 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685824.1 link	n.*372C>G		non_coding_transcript_exon_variant	Exon 4 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*275C>G		non_coding_transcript_exon_variant	Exon 6 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*372C>G		non_coding_transcript_exon_variant	Exon 4 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.557C>G		non_coding_transcript_exon_variant	Exon 5 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000689164.1 link	n.557C>G		non_coding_transcript_exon_variant	Exon 5 of 24			ENSP00000508729.1	A0A8I5KR26
TAF2	ENST00000689919.1 link	n.*275C>G		non_coding_transcript_exon_variant	Exon 6 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.557C>G		non_coding_transcript_exon_variant	Exon 5 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.557C>G		non_coding_transcript_exon_variant	Exon 5 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*213C>G		non_coding_transcript_exon_variant	Exon 4 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*372C>G		non_coding_transcript_exon_variant	Exon 4 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*275C>G		non_coding_transcript_exon_variant	Exon 6 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000685663.1 link	n.*429C>G		3_prime_UTR_variant	Exon 7 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685824.1 link	n.*372C>G		3_prime_UTR_variant	Exon 4 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*275C>G		3_prime_UTR_variant	Exon 6 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*372C>G		3_prime_UTR_variant	Exon 4 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000689919.1 link	n.*275C>G		3_prime_UTR_variant	Exon 6 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000691880.1 link	n.*213C>G		3_prime_UTR_variant	Exon 4 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*372C>G		3_prime_UTR_variant	Exon 4 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*275C>G		3_prime_UTR_variant	Exon 6 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.520+37C>G		intron_variant	Intron 5 of 24			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000688037.1 link	n.139-1856C>G		intron_variant	Intron 2 of 22			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000690031.1 link	n.*238+37C>G		intron_variant	Intron 6 of 9			ENSP00000508549.1	A0A8I5KUD2
TAF2	ENST00000691847.1 link	n.538+19C>G		intron_variant	Intron 5 of 23			ENSP00000509663.1	A0A8I5QJJ6
TAF2	ENST00000692916.1 link	n.419-1856C>G		intron_variant	Intron 4 of 24			ENSP00000509603.1	A0A8I5QJI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 01, 2019

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephaly-thin corpus callosum-intellectual disability syndrome

Uncertain:1

Dec 01, 2013

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

9.9

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.77

Vest4

0.89

MutPred

0.81

Gain of MoRF binding (P = 0.1401);

MVP

0.28

MPC

0.97

ClinPred

0.95

GERP RS

5.8

Varity_R

0.81

gMVP

0.95

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 37

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over