chr8-119731940-G-A

Variant names:

• chr8-119731940-G-A
• NM_003184.4:c.3584C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003184.4(TAF2):​c.3584C>T​(p.Pro1195Leu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.92
• Publications: 0 publications found

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, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37158096).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	NM_003184.4	MANE Select	c.3584C>T	p.Pro1195Leu	missense	Exon 26 of 26	NP_003175.2	Q6P1X5
	TAF2	NM_001437338.1		c.3740C>T	p.Pro1247Leu	missense	Exon 27 of 27	NP_001424267.1	A0A8I5KV60
	TAF2	NM_001438084.1		c.3629C>T	p.Pro1210Leu	missense	Exon 26 of 26	NP_001425013.1	A0A8I5QJR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	ENST00000378164.7	TSL:1 MANE Select	c.3584C>T	p.Pro1195Leu	missense	Exon 26 of 26	ENSP00000367406.2	Q6P1X5
	TAF2	ENST00000686879.1		c.3740C>T	p.Pro1247Leu	missense	Exon 27 of 27	ENSP00000509206.1	A0A8I5KV60
	TAF2	ENST00000685235.1		c.3629C>T	p.Pro1210Leu	missense	Exon 26 of 26	ENSP00000510174.1	A0A8I5QJR0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.90	L
PhyloP100		7.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.44
MPC		0.83
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.29
gMVP		0.30
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr8-120744180;