8-119791397-C-G

Variant names:

• chr8-119791397-C-G
• rs9297605
• NM_003184.4:c.1340G>C

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.1340G>C​(p.Ser447Thr) variant causes a missense change. The variant allele was found at a frequency of 0.692 in 1,612,938 control chromosomes in the GnomAD database, including 388,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38559 hom., cov: 32)
  • Exomes 𝑓: 0.69 (349458 hom.)
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.80
• Publications: 37 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.565472E-7).
• BP6: Variant 8-119791397-C-G is Benign according to our data. Variant chr8-119791397-C-G is described in ClinVar as Benign. ClinVar VariationId is 1165134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	NM_003184.4	MANE Select	c.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	NP_003175.2
	TAF2	NM_001437338.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 27	NP_001424267.1
	TAF2	NM_001438084.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 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.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	ENSP00000367406.2
	TAF2	ENST00000686879.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 27	ENSP00000509206.1
	TAF2	ENST00000685235.1		c.1340G>C	p.Ser447Thr	missense	Exon 11 of 26	ENSP00000510174.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107949 AN: 151850 Hom.: 38530 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.741

GnomAD2 exomes AF: 0.684 AC: 171765 AN: 250970 AF XY: 0.684

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.754

Gnomad EAS exome AF: 0.462

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.705

Gnomad OTH exome AF: 0.702

GnomAD4 exome AF: 0.690 AC: 1007878 AN: 1460970 Hom.: 349458 Cov.: 43 AF XY: 0.689 AC XY: 501054 AN XY: 726798

African (AFR) AF: 0.767 AC: 25660 AN: 33436

American (AMR) AF: 0.691 AC: 30893 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 19653 AN: 26110

East Asian (EAS) AF: 0.448 AC: 17737 AN: 39616

South Asian (SAS) AF: 0.667 AC: 57537 AN: 86222

European-Finnish (FIN) AF: 0.690 AC: 36810 AN: 53346

Middle Eastern (MID) AF: 0.811 AC: 4669 AN: 5758

European-Non Finnish (NFE) AF: 0.695 AC: 772843 AN: 1111464

Other (OTH) AF: 0.698 AC: 42076 AN: 60324

GnomAD4 genome AF: 0.711 AC: 108036 AN: 151968 Hom.: 38559 Cov.: 32 AF XY: 0.709 AC XY: 52659 AN XY: 74246

African (AFR) AF: 0.759 AC: 31460 AN: 41440

American (AMR) AF: 0.727 AC: 11100 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2606 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2384 AN: 5160

South Asian (SAS) AF: 0.659 AC: 3174 AN: 4820

European-Finnish (FIN) AF: 0.689 AC: 7243 AN: 10518

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47589 AN: 67962

Other (OTH) AF: 0.735 AC: 1553 AN: 2114

Alfa AF: 0.692 Hom.: 25511

Bravo AF: 0.715

TwinsUK AF: 0.704 AC: 2611

ALSPAC AF: 0.682 AC: 2629

ESP6500AA AF: 0.769 AC: 3388

ESP6500EA AF: 0.698 AC: 6004

ExAC AF: 0.685 AC: 83114

Asia WGS AF: 0.543 AC: 1886 AN: 3476

EpiCase AF: 0.704

EpiControl AF: 0.718

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.23	T
MetaRNN	Benign	9.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		4.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.087
Sift	Benign	0.64	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.043
MPC		0.37
ClinPred		0.0055	T
GERP RS		3.0
Varity_R		0.073
gMVP		0.40
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9297605; hg19: chr8-120803637; COSMIC: COSV65416628;