Variant 3-121854688-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018456.6(EAF2):c.203G>T(p.Gly68Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

EAF2
NM_018456.6 missense, splice_region

Scores

Splicing: ADA: 0.9767

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.73

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EAF2	NM_018456.6 linkuse as main transcript	c.203G>T	p.Gly68Val	missense_variant, splice_region_variant	3/6	ENST00000273668.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF2	ENST00000273668.7 linkuse as main transcript	c.203G>T	p.Gly68Val	missense_variant, splice_region_variant	3/6	1	NM_018456.6	P1	Q96CJ1-1
EAF2	ENST00000490434.5 linkuse as main transcript	c.202-2323G>T		intron_variant, NMD_transcript_variant		1
EAF2	ENST00000451944.2 linkuse as main transcript	c.203G>T	p.Gly68Val	missense_variant, splice_region_variant	3/6	2
EAF2	ENST00000490477.1 linkuse as main transcript	c.*245G>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	4/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1386182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000408

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:

0.00

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 specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.203G>T (p.G68V) alteration is located in exon 3 (coding exon 3) of the EAF2 gene. This alteration results from a G to T substitution at nucleotide position 203, causing the glycine (G) at amino acid position 68 to be replaced by a valine (V). 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

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.1

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.59

Loss of disorder (P = 0.0587);Loss of disorder (P = 0.0587);

MVP

0.49

MPC

0.54

ClinPred

0.99

GERP RS

5.2

Varity_R

0.89

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.73

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

Other links and lift over