Variant 3-121857126-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018456.6(EAF2):c.454C>T(p.Pro152Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EAF2
NM_018456.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Variant links:

Genes affected

EAF2 (HGNC:23115): (ELL associated factor 2) Enables transcription elongation regulator activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription elongation from RNA polymerase II promoter. Part of transcription elongation factor complex. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

EAF2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24143577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EAF2	NM_018456.6 linkuse as main transcript	c.454C>T	p.Pro152Ser	missense_variant	4/6	ENST00000273668.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF2	ENST00000273668.7 linkuse as main transcript	c.454C>T	p.Pro152Ser	missense_variant	4/6	1	NM_018456.6	P1	Q96CJ1-1
EAF2	ENST00000490434.5 linkuse as main transcript	c.*110C>T		3_prime_UTR_variant, NMD_transcript_variant	3/5	1
EAF2	ENST00000451944.2 linkuse as main transcript	c.454C>T	p.Pro152Ser	missense_variant	4/6	2
EAF2	ENST00000490477.1 linkuse as main transcript	c.*496C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460404

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726582

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.454C>T (p.P152S) alteration is located in exon 4 (coding exon 4) of the EAF2 gene. This alteration results from a C to T substitution at nucleotide position 454, causing the proline (P) at amino acid position 152 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.26

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.20

T;T

Polyphen

1.0

D;.

Vest4

0.42

MutPred

0.26

Gain of phosphorylation at P152 (P = 0.0058);Gain of phosphorylation at P152 (P = 0.0058);

MVP

0.31

MPC

0.50

ClinPred

0.98

GERP RS

3.1

Varity_R

0.30

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over