8-119732159-C-T

Variant names:

• chr8-119732159-C-T
• rs956749
• NM_003184.4:c.3365G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003184.4(TAF2):​c.3365G>A​(p.Ser1122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,613,680 control chromosomes in the GnomAD database, including 5,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (1089 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3921 hom.)
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.19
• Publications: 16 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.4427E-4).
• BP6: Variant 8-119732159-C-T is Benign according to our data. Variant chr8-119732159-C-T is described in ClinVar as Benign. ClinVar VariationId is 1170266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	NM_003184.4	MANE Select	c.3365G>A	p.Ser1122Asn	missense	Exon 26 of 26	NP_003175.2	Q6P1X5
	TAF2	NM_001437338.1		c.3521G>A	p.Ser1174Asn	missense	Exon 27 of 27	NP_001424267.1	A0A8I5KV60
	TAF2	NM_001438084.1		c.3410G>A	p.Ser1137Asn	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.3365G>A	p.Ser1122Asn	missense	Exon 26 of 26	ENSP00000367406.2	Q6P1X5
	TAF2	ENST00000686879.1		c.3521G>A	p.Ser1174Asn	missense	Exon 27 of 27	ENSP00000509206.1	A0A8I5KV60
	TAF2	ENST00000685235.1		c.3410G>A	p.Ser1137Asn	missense	Exon 26 of 26	ENSP00000510174.1	A0A8I5QJR0

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14838 AN: 152078 Hom.: 1089 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0803

GnomAD2 exomes AF: 0.0619 AC: 15569 AN: 251316 AF XY: 0.0590

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.0265

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0751

Gnomad NFE exome AF: 0.0639

Gnomad OTH exome AF: 0.0498

GnomAD4 exome AF: 0.0661 AC: 96625 AN: 1461484 Hom.: 3921 Cov.: 32 AF XY: 0.0650 AC XY: 47251 AN XY: 727076

African (AFR) AF: 0.210 AC: 7041 AN: 33470

American (AMR) AF: 0.0412 AC: 1842 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 668 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0414 AC: 3568 AN: 86254

European-Finnish (FIN) AF: 0.0743 AC: 3965 AN: 53400

Middle Eastern (MID) AF: 0.0489 AC: 282 AN: 5768

European-Non Finnish (NFE) AF: 0.0677 AC: 75240 AN: 1111648

Other (OTH) AF: 0.0664 AC: 4012 AN: 60386

GnomAD4 genome AF: 0.0976 AC: 14850 AN: 152196 Hom.: 1089 Cov.: 33 AF XY: 0.0943 AC XY: 7021 AN XY: 74422

African (AFR) AF: 0.202 AC: 8379 AN: 41512

American (AMR) AF: 0.0404 AC: 618 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0363 AC: 175 AN: 4822

European-Finnish (FIN) AF: 0.0758 AC: 804 AN: 10600

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0664 AC: 4515 AN: 68008

Other (OTH) AF: 0.0795 AC: 168 AN: 2114

Alfa AF: 0.0699 Hom.: 1756

Bravo AF: 0.0989

TwinsUK AF: 0.0701 AC: 260

ALSPAC AF: 0.0664 AC: 256

ESP6500AA AF: 0.208 AC: 918

ESP6500EA AF: 0.0629 AC: 541

ExAC AF: 0.0659 AC: 7996

Asia WGS AF: 0.0250 AC: 88 AN: 3478

EpiCase AF: 0.0564

EpiControl AF: 0.0560

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	TAF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.00084	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.057
Sift	Benign	0.51	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.0050
MPC		0.38
ClinPred		0.00053	T
GERP RS		3.2
Varity_R		0.034
gMVP		0.066
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

dbSNP: rs956749; hg19: chr8-120744399; COSMIC: COSV65418060;