chr8-119819488-T-C

Variant names:

• chr8-119819488-T-C
• rs112002462
• NM_003184.4:c.157A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003184.4(TAF2):​c.157A>G​(p.Ile53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,607,978 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (4 hom.)
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:3
• Conservation: PhyloP100: 2.20
• Publications: 7 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021154523).
• BP6: Variant 8-119819488-T-C is Benign according to our data. Variant chr8-119819488-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 436942.
• BS2: High Homozygotes in GnomAdExome4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF2	NM_003184.4	MANE Select	c.157A>G	p.Ile53Val	missense	Exon 3 of 26	NP_003175.2	Q6P1X5
	TAF2	NM_001437338.1		c.157A>G	p.Ile53Val	missense	Exon 3 of 27	NP_001424267.1	A0A8I5KV60
	TAF2	NM_001438084.1		c.157A>G	p.Ile53Val	missense	Exon 3 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.157A>G	p.Ile53Val	missense	Exon 3 of 26	ENSP00000367406.2	Q6P1X5
	TAF2	ENST00000686879.1		c.157A>G	p.Ile53Val	missense	Exon 3 of 27	ENSP00000509206.1	A0A8I5KV60
	TAF2	ENST00000685235.1		c.157A>G	p.Ile53Val	missense	Exon 3 of 26	ENSP00000510174.1	A0A8I5QJR0

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00101 AC: 250 AN: 247548 AF XY: 0.000939

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000221

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00157 AC: 2286 AN: 1455676 Hom.: 4 Cov.: 31 AF XY: 0.00153 AC XY: 1105 AN XY: 724538

African (AFR) AF: 0.000179 AC: 6 AN: 33442

American (AMR) AF: 0.000380 AC: 17 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.000812 AC: 70 AN: 86226

European-Finnish (FIN) AF: 0.000308 AC: 15 AN: 48648

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5756

European-Non Finnish (NFE) AF: 0.00182 AC: 2023 AN: 1110908

Other (OTH) AF: 0.00244 AC: 147 AN: 60296

GnomAD4 genome AF: 0.00117 AC: 178 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00111 AC XY: 83 AN XY: 74490

African (AFR) AF: 0.000289 AC: 12 AN: 41578

American (AMR) AF: 0.000588 AC: 9 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00221 AC: 150 AN: 68012

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00151 Hom.: 1

Bravo AF: 0.00114

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.000947 AC: 115

Asia WGS AF: 0.000579 AC: 2 AN: 3468

EpiCase AF: 0.00158

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	not provided (3)
-	1	1	not specified (2)
-	1	-	Microcephaly-thin corpus callosum-intellectual disability syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.15
Sift	Benign	0.20	T
Sift4G	Benign	0.18	T
Polyphen		0.84	P
Vest4		0.24
MVP		0.14
MPC		0.37
ClinPred		0.025	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.39
Mutation Taster		=96/4	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: rs112002462; hg19: chr8-120831728;