dbSNP rs61753747: TAF2:p.Lys1157Lys (chr8-119732053-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_003184.4(TAF2):c.3471G>A(p.Lys1157Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.0192 in 1,614,052 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 31 hom., cov: 32)

Exomes 𝑓: 0.020 ( 356 hom. )

Consequence

TAF2
NM_003184.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.30

Publications

5 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

TAF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 8-119732053-C-T is Benign according to our data. Variant chr8-119732053-C-T is described in ClinVar as Benign. ClinVar VariationId is 1169029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0157 (2384/152242) while in subpopulation NFE AF = 0.0228 (1548/68020). AF 95% confidence interval is 0.0218. There are 31 homozygotes in GnomAd4. There are 1142 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF2	NM_003184.4	MANE Select	c.3471G>A	p.Lys1157Lys	synonymous	Exon 26 of 26	NP_003175.2	Q6P1X5
TAF2	NM_001437338.1		c.3627G>A	p.Lys1209Lys	synonymous	Exon 27 of 27	NP_001424267.1	A0A8I5KV60
TAF2	NM_001438084.1		c.3516G>A	p.Lys1172Lys	synonymous	Exon 26 of 26	NP_001425013.1	A0A8I5QJR0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF2	ENST00000378164.7	TSL:1 MANE Select	c.3471G>A	p.Lys1157Lys	synonymous	Exon 26 of 26	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1		c.3627G>A	p.Lys1209Lys	synonymous	Exon 27 of 27	ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1		c.3516G>A	p.Lys1172Lys	synonymous	Exon 26 of 26	ENSP00000510174.1	A0A8I5QJR0

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2383

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00389

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0165

AC:

4158

AN:

251322

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.00746

Gnomad ASJ exome

AF:

0.0568

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0179

GnomAD4 exome

AF:

0.0196

AC:

28598

AN:

1461810

Hom.:

356

Cov.:

AF XY:

0.0191

AC XY:

13905

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.00361

AC:

121

AN:

33480

American (AMR)

AF:

0.00756

AC:

338

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0582

AC:

1522

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00294

AC:

254

AN:

86254

European-Finnish (FIN)

AF:

0.0183

AC:

977

AN:

53412

Middle Eastern (MID)

AF:

0.0291

AC:

168

AN:

5766

European-Non Finnish (NFE)

AF:

0.0216

AC:

24034

AN:

1111944

Other (OTH)

AF:

0.0196

AC:

1183

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1502

3004

4506

6008

7510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0157

AC:

2384

AN:

152242

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1142

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00388

AC:

161

AN:

41540

American (AMR)

AF:

0.0126

AC:

193

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0533

AC:

185

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00270

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0188

AC:

200

AN:

10612

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0228

AC:

1548

AN:

68020

Other (OTH)

AF:

0.0109

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

120

240

361

481

601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0227

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0237

EpiControl

AF:

0.0255

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Microcephaly-thin corpus callosum-intellectual disability syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

9.2

(source)

DANN

Benign

0.74

PhyloP100

6.3

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over