Genetic Variant ENO2:c.865+124C>A (chr12-6919887-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001975.3(ENO2):c.865+124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,066,340 control chromosomes in the GnomAD database, including 1,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.051 ( 574 hom., cov: 30)

Exomes 𝑓: 0.016 ( 1297 hom. )

Consequence

ENO2
NM_001975.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

Publications

3 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001975.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO2	NM_001975.3	MANE Select	c.865+124C>A		intron	N/A	NP_001966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENO2	ENST00000229277.6	TSL:1 MANE Select	c.865+124C>A	intron	N/A	ENSP00000229277.1
ENO2	ENST00000535366.5	TSL:1	c.865+124C>A	intron	N/A	ENSP00000437402.1
ENO2	ENST00000541477.5	TSL:2	c.865+124C>A	intron	N/A	ENSP00000438873.1

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7715

AN:

151892

Hom.:

569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0271

Gnomad ASJ

AF:

0.00693

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.0485

GnomAD4 exome

AF:

0.0161

AC:

14684

AN:

914330

Hom.:

1297

AF XY:

0.0153

AC XY:

7000

AN XY:

458844

show subpopulations

African (AFR)

AF:

0.145

AC:

3139

AN:

21580

American (AMR)

AF:

0.0164

AC:

427

AN:

26000

Ashkenazi Jewish (ASJ)

AF:

0.00860

AC:

155

AN:

18022

East Asian (EAS)

AF:

0.237

AC:

7947

AN:

33476

South Asian (SAS)

AF:

0.0108

AC:

642

AN:

59322

European-Finnish (FIN)

AF:

0.000138

AC:

AN:

36228

Middle Eastern (MID)

AF:

0.0330

AC:

AN:

2908

European-Non Finnish (NFE)

AF:

0.00178

AC:

1201

AN:

675238

Other (OTH)

AF:

0.0258

AC:

1072

AN:

41556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

632

1264

1896

2528

3160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0509

AC:

7732

AN:

152010

Hom.:

574

Cov.:

AF XY:

0.0505

AC XY:

3754

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.141

AC:

5855

AN:

41428

American (AMR)

AF:

0.0269

AC:

411

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00693

AC:

AN:

3464

East Asian (EAS)

AF:

0.218

AC:

1120

AN:

5132

South Asian (SAS)

AF:

0.0129

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00210

AC:

143

AN:

67984

Other (OTH)

AF:

0.0490

AC:

103

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

328

656

985

1313

1641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0178

Hom.:

Bravo

AF:

0.0587

Asia WGS

AF:

0.0810

AC:

283

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

(source)

DANN

Benign

0.62

PhyloP100

-0.019

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over