Genetic Variant EGLN2:c.-681_-678delGTCT (chr19-40799888-CTCTG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000593726(EGLN2):c.-681_-678delGTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 144,186 control chromosomes in the GnomAD database, including 12,392 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12386 hom., cov: 0)

Exomes 𝑓: 0.24 ( 6 hom. )

Consequence

EGLN2
ENST00000593726 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.344

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-40799888-CTCTG-C is Benign according to our data. Variant chr19-40799888-CTCTG-C is described in ClinVar as [Benign]. Clinvar id is 1228205.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EGLN2	NM_080732.4 link	c.-234-447_-234-444delGTCT	intron_variant	Intron 1 of 5	ENST00000303961.9	NP_542770.2	Q96KS0-1A0A024R0R2
EGLN2	NM_053046.4 link	c.-235+254_-235+257delGTCT	intron_variant	Intron 1 of 5		NP_444274.1	Q96KS0-1A0A024R0R2
RAB4B-EGLN2	NR_037791.1 link	n.815-447_815-444delGTCT	intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9 link	c.-234-447_-234-444delGTCT		intron_variant	Intron 1 of 5	1	NM_080732.4	ENSP00000307080.3		Q96KS0-1
RAB4B-EGLN2	ENST00000594136.2 link	n.16-447_16-444delGTCT		intron_variant	Intron 7 of 11	2		ENSP00000469872.1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

56586

AN:

143960

Hom.:

12385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.236

AC:

AN:

110

Hom.:

AF XY:

0.206

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.441

Gnomad4 NFE exome

AF:

0.0385

Gnomad4 OTH exome

AF:

0.600

GnomAD4 genome

AF:

0.393

AC:

56612

AN:

144076

Hom.:

12386

Cov.:

AF XY:

0.391

AC XY:

27198

AN XY:

69556

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.496

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.574

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.447

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.394

Hom.:

1361

Asia WGS

AF:

0.512

AC:

1770

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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