Variant 12-6917050-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001975.3(ENO2):c.253G>A(p.Val85Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,212 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ENO2
NM_001975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

ENO2 (HGNC:3353): (enolase 2) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates. [provided by RefSeq, Jul 2008]

ENO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28887075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO2	NM_001975.3 linkuse as main transcript	c.253G>A	p.Val85Met	missense_variant	5/12	ENST00000229277.6	NP_001966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENO2	ENST00000229277.6 linkuse as main transcript	c.253G>A	p.Val85Met	missense_variant	5/12	1	NM_001975.3	ENSP00000229277	P1	P09104-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

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

Aug 10, 2021

The c.253G>A (p.V85M) alteration is located in exon 5 (coding exon 4) of the ENO2 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the valine (V) at amino acid position 85 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;T;T;.;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;.;D;D;.

M_CAP

Benign

0.029

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

.;L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.010

D;D;D;T;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.017

.;B;B;.;B

Vest4

0.47, 0.43, 0.46

MutPred

0.34

Gain of ubiquitination at K89 (P = 0.068);Gain of ubiquitination at K89 (P = 0.068);Gain of ubiquitination at K89 (P = 0.068);Gain of ubiquitination at K89 (P = 0.068);Gain of ubiquitination at K89 (P = 0.068);

MVP

0.52

MPC

0.88

ClinPred

0.90

GERP RS

5.2

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.61

gMVP

0.60

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