dbSNP rs138867869: EGLN2:c.-649_-648delTC (chr19-40799920-ACT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000593726.5(EGLN2):c.-649_-648delTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 253 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EGLN2
ENST00000593726.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0600

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 19-40799920-ACT-A is Benign according to our data. Variant chr19-40799920-ACT-A is described in ClinVar as Benign. ClinVar VariationId is 1252635.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593726.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EGLN2	NM_080732.4	MANE Select	c.-234-415_-234-414delTC	intron	N/A	NP_542770.2	Q96KS0-1
EGLN2	NM_053046.4		c.-235+286_-235+287delTC	intron	N/A	NP_444274.1	Q96KS0-1
RAB4B-EGLN2	NR_037791.1		n.815-415_815-414delTC	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EGLN2	ENST00000593726.5	TSL:1	c.-649_-648delTC	5_prime_UTR	Exon 1 of 5	ENSP00000469686.1	Q96KS0-1
EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.-234-415_-234-414delTC	intron	N/A	ENSP00000307080.3	Q96KS0-1
EGLN2	ENST00000406058.6	TSL:1	c.-235+286_-235+287delTC	intron	N/A	ENSP00000385253.1	Q96KS0-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

7863

AN:

62308

Hom.:

252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.00150

Gnomad SAS

AF:

0.0417

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.195

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.151

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.126

AC:

7872

AN:

62348

Hom.:

253

Cov.:

AF XY:

0.123

AC XY:

3731

AN XY:

30440

show subpopulations

African (AFR)

AF:

0.143

AC:

2389

AN:

16708

American (AMR)

AF:

0.120

AC:

732

AN:

6076

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

417

AN:

1758

East Asian (EAS)

AF:

0.00150

AC:

AN:

1996

South Asian (SAS)

AF:

0.0411

AC:

AN:

1266

European-Finnish (FIN)

AF:

0.120

AC:

434

AN:

3626

Middle Eastern (MID)

AF:

0.218

AC:

AN:

124

European-Non Finnish (NFE)

AF:

0.123

AC:

3627

AN:

29444

Other (OTH)

AF:

0.150

AC:

129

AN:

860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

331

662

993

1324

1655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.00776

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.060

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over