Genetic Variant EGLN2:n.197A>G (chr19-40804666-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000593445.5(EGLN2):n.197A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,242 control chromosomes in the GnomAD database, including 7,948 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 0.29 ( 7938 hom., cov: 32)

Exomes 𝑓: 0.30 ( 10 hom. )

Consequence

EGLN2
ENST00000593445.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

Publications

82 publications found

Variant links:

Genes affected

EGLN2 (HGNC:14660): (egl-9 family hypoxia inducible factor 2) The hypoxia inducible factor (HIF) is a transcriptional complex that is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degration by prolyl hydroxylation. This gene encodes an enzyme responsible for this post-translational modification. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream RAB4B (RAB4B, member RAS oncogene family) gene. [provided by RefSeq, Feb 2011]

EGLN2 links:

RAB4B-EGLN2 (HGNC:44465): (RAB4B-EGLN2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RAB4B (RAB4B, member RAS oncogene family) and EGLN2 (egl nine homolog 2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

RAB4B-EGLN2 links:

ENSG00000268797 (HGNC:):

ENSG00000268797 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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
EGLN2	NM_080732.4 link	c.844-1889A>G	intron_variant	Intron 2 of 5	ENST00000303961.9	NP_542770.2
EGLN2	NM_053046.4 link	c.844-1889A>G	intron_variant	Intron 2 of 5		NP_444274.1
RAB4B-EGLN2	NR_037791.1 link	n.1892-1889A>G	intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EGLN2	ENST00000303961.9 link	c.844-1889A>G	intron_variant	Intron 2 of 5	1	NM_080732.4	ENSP00000307080.3
RAB4B-EGLN2	ENST00000594136.2 link	n.*1093-1889A>G	intron_variant	Intron 8 of 11	2		ENSP00000469872.1
ENSG00000268797	ENST00000601627.1 link	n.117+3251A>G	intron_variant	Intron 1 of 3	3		ENSP00000469533.1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43958

AN:

151986

Hom.:

7931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0751

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.304

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.316

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.389

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.341

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.289

AC:

43977

AN:

152104

Hom.:

7938

Cov.:

AF XY:

0.292

AC XY:

21698

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0749

AC:

3109

AN:

41504

American (AMR)

AF:

0.430

AC:

6570

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1030

AN:

3470

East Asian (EAS)

AF:

0.373

AC:

1926

AN:

5164

South Asian (SAS)

AF:

0.378

AC:

1825

AN:

4826

European-Finnish (FIN)

AF:

0.359

AC:

3794

AN:

10570

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24516

AN:

67966

Other (OTH)

AF:

0.324

AC:

685

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1475

2950

4424

5899

7374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.340

Hom.:

40256

Bravo

AF:

0.286

Asia WGS

AF:

0.394

AC:

1369

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.059

(source)

DANN

Benign

0.80

PhyloP100

-2.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over