17-37474627-G-C

Position:

• chr17-37474627-G-C

Variant summary

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

The NM_001166105.3(TADA2A):​c.1144G>C​(p.Glu382Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TADA2A NM_001166105.3 missense, splice_region
• Scores: Splicing: ADA: 0.9627
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.64

Genes affected

TADA2A (HGNC:11531): (transcriptional adaptor 2A) Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated gene transcription by interacting functionally with the general transcription machinery bound at the basal promoter. Adaptor proteins are usually required for this activation, possibly to acetylate and destabilize nucleosomes, thereby relieving chromatin constraints at the promoter. The protein encoded by this gene is a transcriptional activator adaptor and has been found to be part of the PCAF histone acetylase complex. Several alternatively spliced transcript variants encoding different isoforms of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2009]

TADA2A (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
TADA2A	NM_001166105.3	c.1144G>C	p.Glu382Gln	missense_variant, splice_region_variant	15/16	ENST00000615182.5	NP_001159577.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TADA2A	ENST00000615182.5	c.1144G>C	p.Glu382Gln	missense_variant, splice_region_variant	15/16	5	NM_001166105.3	ENSP00000481091.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.1144G>C (p.E382Q) alteration is located in exon 15 (coding exon 14) of the TADA2A gene. This alteration results from a G to C substitution at nucleotide position 1144, causing the glutamic acid (E) at amino acid position 382 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.74	T
Sift4G	Benign	0.11	T;T
Vest4		0.70
MutPred		0.40		Loss of ubiquitination at K379 (P = 0.0597);Loss of ubiquitination at K379 (P = 0.0597);
MVP		0.48
ClinPred		0.92	D
GERP RS		5.8
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.96
dbscSNV1_RF	Pathogenic	0.80
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.

Other links and lift over

hg19: chr17-35834732;