8-119791397-C-T

Position:

• chr8-119791397-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003184.4(TAF2):​c.1340G>A​(p.Ser447Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S447T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TAF2. . Gene score misZ 2.7836 (greater than the threshold 3.09). Trascript score misZ 3.5113 (greater than threshold 3.09). GenCC has associacion of gene with microcephaly-thin corpus callosum-intellectual disability syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.11212647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4	c.1340G>A	p.Ser447Asn	missense_variant	11/26	ENST00000378164.7	NP_003175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF2	ENST00000378164.7	c.1340G>A	p.Ser447Asn	missense_variant	11/26	1	NM_003184.4	ENSP00000367406.2
TAF2	ENST00000686879.1	c.1340G>A	p.Ser447Asn	missense_variant	11/27			ENSP00000509206.1
TAF2	ENST00000685235.1	c.1340G>A	p.Ser447Asn	missense_variant	11/26			ENSP00000510174.1
TAF2	ENST00000688645.1	c.1340G>A	p.Ser447Asn	missense_variant	11/25			ENSP00000509978.1
TAF2	ENST00000523904.2	c.1226G>A	p.Ser409Asn	missense_variant	10/25	3		ENSP00000430832.2
TAF2	ENST00000690144.1	c.1340G>A	p.Ser447Asn	missense_variant	11/26			ENSP00000510548.1
TAF2	ENST00000685202.1	n.1340G>A		non_coding_transcript_exon_variant	11/27			ENSP00000509214.1
TAF2	ENST00000685503.1	n.*732G>A		non_coding_transcript_exon_variant	11/26			ENSP00000509198.1
TAF2	ENST00000685663.1	n.*1212G>A		non_coding_transcript_exon_variant	13/28			ENSP00000508988.1
TAF2	ENST00000685684.1	n.*2807G>A		non_coding_transcript_exon_variant	10/25			ENSP00000509441.1
TAF2	ENST00000685824.1	n.*1041G>A		non_coding_transcript_exon_variant	9/24			ENSP00000510262.1
TAF2	ENST00000685876.1	n.*1058G>A		non_coding_transcript_exon_variant	12/27			ENSP00000510493.1
TAF2	ENST00000685993.1	n.*1155G>A		non_coding_transcript_exon_variant	10/25			ENSP00000510102.1
TAF2	ENST00000686098.1	n.1254G>A		non_coding_transcript_exon_variant	10/25			ENSP00000509102.1
TAF2	ENST00000688037.1	n.*759G>A		non_coding_transcript_exon_variant	8/23			ENSP00000510169.1
TAF2	ENST00000689164.1	n.1140G>A		non_coding_transcript_exon_variant	9/24			ENSP00000508729.1
TAF2	ENST00000689919.1	n.*1058G>A		non_coding_transcript_exon_variant	12/26			ENSP00000510768.1
TAF2	ENST00000690808.1	n.*576G>A		non_coding_transcript_exon_variant	11/26			ENSP00000509791.1
TAF2	ENST00000690922.1	n.1340G>A		non_coding_transcript_exon_variant	11/26			ENSP00000509498.1
TAF2	ENST00000691847.1	n.*641G>A		non_coding_transcript_exon_variant	10/24			ENSP00000509663.1
TAF2	ENST00000691880.1	n.*996G>A		non_coding_transcript_exon_variant	10/25			ENSP00000508515.1
TAF2	ENST00000692518.1	n.*1041G>A		non_coding_transcript_exon_variant	9/25			ENSP00000508959.1
TAF2	ENST00000692707.1	n.*1208G>A		non_coding_transcript_exon_variant	13/28			ENSP00000509024.1
TAF2	ENST00000692916.1	n.*727G>A		non_coding_transcript_exon_variant	10/25			ENSP00000509603.1
TAF2	ENST00000685503.1	n.*732G>A		3_prime_UTR_variant	11/26			ENSP00000509198.1
TAF2	ENST00000685663.1	n.*1212G>A		3_prime_UTR_variant	13/28			ENSP00000508988.1
TAF2	ENST00000685684.1	n.*2807G>A		3_prime_UTR_variant	10/25			ENSP00000509441.1
TAF2	ENST00000685824.1	n.*1041G>A		3_prime_UTR_variant	9/24			ENSP00000510262.1
TAF2	ENST00000685876.1	n.*1058G>A		3_prime_UTR_variant	12/27			ENSP00000510493.1
TAF2	ENST00000685993.1	n.*1155G>A		3_prime_UTR_variant	10/25			ENSP00000510102.1
TAF2	ENST00000688037.1	n.*759G>A		3_prime_UTR_variant	8/23			ENSP00000510169.1
TAF2	ENST00000689919.1	n.*1058G>A		3_prime_UTR_variant	12/26			ENSP00000510768.1
TAF2	ENST00000690808.1	n.*576G>A		3_prime_UTR_variant	11/26			ENSP00000509791.1
TAF2	ENST00000691847.1	n.*641G>A		3_prime_UTR_variant	10/24			ENSP00000509663.1
TAF2	ENST00000691880.1	n.*996G>A		3_prime_UTR_variant	10/25			ENSP00000508515.1
TAF2	ENST00000692518.1	n.*1041G>A		3_prime_UTR_variant	9/25			ENSP00000508959.1
TAF2	ENST00000692707.1	n.*1208G>A		3_prime_UTR_variant	13/28			ENSP00000509024.1
TAF2	ENST00000692916.1	n.*727G>A		3_prime_UTR_variant	10/25			ENSP00000509603.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250970 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135624

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461456 Hom.: 0 Cov.: 43 AF XY: 0.00000138 AC XY: 1 AN XY: 727030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.088
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.077
MutPred		0.68		Loss of catalytic residue at S447 (P = 0.1688);
MVP		0.13
MPC		0.38
ClinPred		0.23	T
GERP RS		3.0
Varity_R		0.053
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs9297605; hg19: chr8-120803637;