20-64071907-T-A

Position:

• chr20-64071907-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000343484.10(TCEA2):​c.857T>A​(p.Phe286Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCEA2 ENST00000343484.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97

Genes affected

TCEA2 (HGNC:11614): (transcription elongation factor A2) The protein encoded by this gene is found in the nucleus, where it functions as an SII class transcription elongation factor. Elongation factors in this class are responsible for releasing RNA polymerase II ternary complexes from transcriptional arrest at template-encoded arresting sites. The encoded protein has been shown to interact with general transcription factor IIB, a basal transcription factor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TCEA2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEA2	NM_003195.6	c.857T>A	p.Phe286Tyr	missense_variant	9/10	ENST00000343484.10	NP_003186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEA2	ENST00000343484.10	c.857T>A	p.Phe286Tyr	missense_variant	9/10	1	NM_003195.6	ENSP00000343515.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Mar 22, 2023

The c.857T>A (p.F286Y) alteration is located in exon 9 (coding exon 9) of the TCEA2 gene. This alteration results from a T to A substitution at nucleotide position 857, causing the phenylalanine (F) at amino acid position 286 to be replaced by a tyrosine (Y). 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;T;T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	.;M;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.033	D;D;D
Sift4G	Uncertain	0.036	D;D;D
Polyphen		0.24	.;B;.
Vest4		0.44
MutPred		0.91		.;Gain of phosphorylation at F286 (P = 0.0884);.;
MVP		0.33
MPC		0.81
ClinPred		0.97	D
GERP RS		1.5
Varity_R		0.20
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-62703260;