Variant chr19-40799835-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000593726.5(EGLN2):c.-738A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 150,188 control chromosomes in the GnomAD database, including 7,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7543 hom., cov: 28)

Exomes 𝑓: 0.27 ( 16 hom. )

Consequence

EGLN2
ENST00000593726.5 5_prime_UTR

Scores

Splicing: ADA: 0.0001602

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.544

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:):

RAB4B-EGLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-40799835-A-G is Benign according to our data. Variant chr19-40799835-A-G is described in ClinVar as [Benign]. Clinvar id is 1228041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
EGLN2	NM_080732.4 linkuse as main transcript	c.-234-504A>G	intron_variant	ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1 linkuse as main transcript	n.815-504A>G	intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4 linkuse as main transcript	c.-235+197A>G	intron_variant		NP_444274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9 linkuse as main transcript	c.-234-504A>G		intron_variant		1	NM_080732.4	ENSP00000307080	P1	Q96KS0-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

44405

AN:

149670

Hom.:

7524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.0937

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.266

AC:

107

AN:

402

Hom.:

Cov.:

AF XY:

0.281

AC XY:

AN XY:

274

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.273

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.297

AC:

44465

AN:

149786

Hom.:

7543

Cov.:

AF XY:

0.295

AC XY:

21505

AN XY:

72958

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.0939

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.236

Hom.:

5726

Bravo

AF:

0.301

Asia WGS

AF:

0.188

AC:

654

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.036

SpliceAI score (max)

0.15

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