8-119791397-C-G

Position:

• chr8-119791397-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -19 ACMG points.

• 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=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 id is 1165134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-119791397-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4	c.1340G>C	p.Ser447Thr	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>C	p.Ser447Thr	missense_variant	11/26	1	NM_003184.4	ENSP00000367406.2
TAF2	ENST00000686879.1	c.1340G>C	p.Ser447Thr	missense_variant	11/27			ENSP00000509206.1
TAF2	ENST00000685235.1	c.1340G>C	p.Ser447Thr	missense_variant	11/26			ENSP00000510174.1
TAF2	ENST00000688645.1	c.1340G>C	p.Ser447Thr	missense_variant	11/25			ENSP00000509978.1
TAF2	ENST00000523904.2	c.1226G>C	p.Ser409Thr	missense_variant	10/25	3		ENSP00000430832.2
TAF2	ENST00000690144.1	c.1340G>C	p.Ser447Thr	missense_variant	11/26			ENSP00000510548.1
TAF2	ENST00000685202.1	n.1340G>C		non_coding_transcript_exon_variant	11/27			ENSP00000509214.1
TAF2	ENST00000685503.1	n.*732G>C		non_coding_transcript_exon_variant	11/26			ENSP00000509198.1
TAF2	ENST00000685663.1	n.*1212G>C		non_coding_transcript_exon_variant	13/28			ENSP00000508988.1
TAF2	ENST00000685684.1	n.*2807G>C		non_coding_transcript_exon_variant	10/25			ENSP00000509441.1
TAF2	ENST00000685824.1	n.*1041G>C		non_coding_transcript_exon_variant	9/24			ENSP00000510262.1
TAF2	ENST00000685876.1	n.*1058G>C		non_coding_transcript_exon_variant	12/27			ENSP00000510493.1
TAF2	ENST00000685993.1	n.*1155G>C		non_coding_transcript_exon_variant	10/25			ENSP00000510102.1
TAF2	ENST00000686098.1	n.1254G>C		non_coding_transcript_exon_variant	10/25			ENSP00000509102.1
TAF2	ENST00000688037.1	n.*759G>C		non_coding_transcript_exon_variant	8/23			ENSP00000510169.1
TAF2	ENST00000689164.1	n.1140G>C		non_coding_transcript_exon_variant	9/24			ENSP00000508729.1
TAF2	ENST00000689919.1	n.*1058G>C		non_coding_transcript_exon_variant	12/26			ENSP00000510768.1
TAF2	ENST00000690808.1	n.*576G>C		non_coding_transcript_exon_variant	11/26			ENSP00000509791.1
TAF2	ENST00000690922.1	n.1340G>C		non_coding_transcript_exon_variant	11/26			ENSP00000509498.1
TAF2	ENST00000691847.1	n.*641G>C		non_coding_transcript_exon_variant	10/24			ENSP00000509663.1
TAF2	ENST00000691880.1	n.*996G>C		non_coding_transcript_exon_variant	10/25			ENSP00000508515.1
TAF2	ENST00000692518.1	n.*1041G>C		non_coding_transcript_exon_variant	9/25			ENSP00000508959.1
TAF2	ENST00000692707.1	n.*1208G>C		non_coding_transcript_exon_variant	13/28			ENSP00000509024.1
TAF2	ENST00000692916.1	n.*727G>C		non_coding_transcript_exon_variant	10/25			ENSP00000509603.1
TAF2	ENST00000685503.1	n.*732G>C		3_prime_UTR_variant	11/26			ENSP00000509198.1
TAF2	ENST00000685663.1	n.*1212G>C		3_prime_UTR_variant	13/28			ENSP00000508988.1
TAF2	ENST00000685684.1	n.*2807G>C		3_prime_UTR_variant	10/25			ENSP00000509441.1
TAF2	ENST00000685824.1	n.*1041G>C		3_prime_UTR_variant	9/24			ENSP00000510262.1
TAF2	ENST00000685876.1	n.*1058G>C		3_prime_UTR_variant	12/27			ENSP00000510493.1
TAF2	ENST00000685993.1	n.*1155G>C		3_prime_UTR_variant	10/25			ENSP00000510102.1
TAF2	ENST00000688037.1	n.*759G>C		3_prime_UTR_variant	8/23			ENSP00000510169.1
TAF2	ENST00000689919.1	n.*1058G>C		3_prime_UTR_variant	12/26			ENSP00000510768.1
TAF2	ENST00000690808.1	n.*576G>C		3_prime_UTR_variant	11/26			ENSP00000509791.1
TAF2	ENST00000691847.1	n.*641G>C		3_prime_UTR_variant	10/24			ENSP00000509663.1
TAF2	ENST00000691880.1	n.*996G>C		3_prime_UTR_variant	10/25			ENSP00000508515.1
TAF2	ENST00000692518.1	n.*1041G>C		3_prime_UTR_variant	9/25			ENSP00000508959.1
TAF2	ENST00000692707.1	n.*1208G>C		3_prime_UTR_variant	13/28			ENSP00000509024.1
TAF2	ENST00000692916.1	n.*727G>C		3_prime_UTR_variant	10/25			ENSP00000509603.1

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

GnomAD3 exomes AF: 0.684 AC: 171765 AN: 250970 Hom.: 59532 AF XY: 0.684 AC XY: 92723 AN XY: 135624

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 SAS exome AF: 0.669

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

Gnomad4 AFR exome AF: 0.767

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.753

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.698

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

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.735

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

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
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

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; COSMIC: COSV65416628;