19-40799920-ACT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000593726.5(EGLN2):c.-649_-648del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0600

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]

RAB4B-EGLN2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN2	NM_080732.4	c.-234-415_-234-414del		intron_variant		ENST00000303961.9
RAB4B-EGLN2	NR_037791.1	n.815-415_815-414del		intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4	c.-235+286_-235+287del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN2	ENST00000303961.9	c.-234-415_-234-414del		intron_variant		1	NM_080732.4	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 7863 AN: 62308 Hom.: 252 Cov.: 0

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: 0 AN: 30 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.126 AC: 7872 AN: 62348 Hom.: 253 Cov.: 0 AF XY: 0.123 AC XY: 3731 AN XY: 30440

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.00150

Gnomad4 SAS AF: 0.0411

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.150

Alfa AF: 0.00776 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs138867869; hg19: chr19-41305825;