8-119788818-T-A

Variant names:

• chr8-119788818-T-A
• rs149772375
• NM_003184.4:c.1655A>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003184.4(TAF2):​c.1655A>T​(p.Tyr552Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00243 in 1,613,806 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (14 hom.)
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 6.27
• Publications: 5 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, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008978754).
• BP6: Variant 8-119788818-T-A is Benign according to our data. Variant chr8-119788818-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 436940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	NM_003184.4	MANE Select	c.1655A>T	p.Tyr552Phe	missense	Exon 13 of 26	NP_003175.2
	TAF2	NM_001437338.1		c.1655A>T	p.Tyr552Phe	missense	Exon 13 of 27	NP_001424267.1
	TAF2	NM_001438084.1		c.1655A>T	p.Tyr552Phe	missense	Exon 13 of 26	NP_001425013.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	ENST00000378164.7	TSL:1 MANE Select	c.1655A>T	p.Tyr552Phe	missense	Exon 13 of 26	ENSP00000367406.2
	TAF2	ENST00000686879.1		c.1655A>T	p.Tyr552Phe	missense	Exon 13 of 27	ENSP00000509206.1
	TAF2	ENST00000685235.1		c.1655A>T	p.Tyr552Phe	missense	Exon 13 of 26	ENSP00000510174.1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152150 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00266 AC: 669 AN: 251358 AF XY: 0.00260

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00572

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00280

Gnomad OTH exome AF: 0.00914

GnomAD4 exome AF: 0.00249 AC: 3634 AN: 1461538 Hom.: 14 Cov.: 30 AF XY: 0.00251 AC XY: 1828 AN XY: 727096

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.00601 AC: 269 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00742 AC: 194 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000974 AC: 84 AN: 86252

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53416

Middle Eastern (MID) AF: 0.00642 AC: 37 AN: 5762

European-Non Finnish (NFE) AF: 0.00250 AC: 2783 AN: 1111742

Other (OTH) AF: 0.00363 AC: 219 AN: 60384

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152268 Hom.: 1 Cov.: 31 AF XY: 0.00167 AC XY: 124 AN XY: 74458

African (AFR) AF: 0.000337 AC: 14 AN: 41580

American (AMR) AF: 0.00321 AC: 49 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00253 AC: 172 AN: 68018

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00240 Hom.: 1

Bravo AF: 0.00237

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00259 AC: 314

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TAF2: BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Aug 13, 2018

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Microcephaly-thin corpus callosum-intellectual disability syndrome Benign:1

Feb 10, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.062
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.15
Sift	Benign	0.67	T
Sift4G	Benign	0.68	T
Polyphen		0.0040	B
Vest4		0.67
MVP		0.33
MPC		0.37
ClinPred		0.026	T
GERP RS		5.6
Varity_R		0.33
gMVP		0.35
Mutation Taster		=92/8	polymorphism

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: rs149772375; hg19: chr8-120801058;