Genetic Variant NM_003184.4:c.3533dupA (chr8-119731990-C-CT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003184.4(TAF2):c.3533dupA(p.Glu1179GlyfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TAF2
NM_003184.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.3533dupA	p.Glu1179GlyfsTer40	frameshift_variant	Exon 26 of 26	ENST00000378164.7	NP_003175.2	Q6P1X5B3KMD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAF2	ENST00000378164.7 link	c.3533dupA	p.Glu1179GlyfsTer40	frameshift_variant	Exon 26 of 26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.3689dupA	p.Glu1231GlyfsTer40	frameshift_variant	Exon 27 of 27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.3578dupA	p.Glu1194GlyfsTer40	frameshift_variant	Exon 26 of 26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.3422dupA	p.Glu1142GlyfsTer40	frameshift_variant	Exon 25 of 25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.3419dupA	p.Glu1141GlyfsTer40	frameshift_variant	Exon 25 of 25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144 link	c.*664dupA		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.*1058dupA		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2925dupA		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3405dupA		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*5000dupA		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3234dupA		non_coding_transcript_exon_variant	Exon 24 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3251dupA		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3348dupA		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2178dupA		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2952dupA		non_coding_transcript_exon_variant	Exon 23 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3140dupA		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2769dupA		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1945dupA		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3189dupA		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3399dupA		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3401dupA		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2920dupA		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685202.1 link	n.*1058dupA		3_prime_UTR_variant	Exon 27 of 27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2925dupA		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3405dupA		3_prime_UTR_variant	Exon 28 of 28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*5000dupA		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3234dupA		3_prime_UTR_variant	Exon 24 of 24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3251dupA		3_prime_UTR_variant	Exon 27 of 27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3348dupA		3_prime_UTR_variant	Exon 25 of 25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2178dupA		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2952dupA		3_prime_UTR_variant	Exon 23 of 23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3140dupA		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2769dupA		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1945dupA		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3189dupA		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3399dupA		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3401dupA		3_prime_UTR_variant	Exon 28 of 28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2920dupA		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000689164.1 link	n.*4151dupA		downstream_gene_variant				ENSP00000508729.1	A0A8I5KR26

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change results in a frameshift in the TAF2 gene (p.Glu1179Glyfs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acid(s) of the TAF2 protein and extend the protein by 18 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2018901). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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