19-40800316-CT-C

Variant summary

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

The ENST00000593726.5(EGLN2):c.-246del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 384,246 control chromosomes in the GnomAD database, including 8,838 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (6458 hom., cov: 21)
  • Exomes 𝑓: 0.22 (2380 hom.)
• Consequence: EGLN2 ENST00000593726.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329

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 19-40800316-CT-C is Benign according to our data. Variant chr19-40800316-CT-C is described in ClinVar as [Benign]. Clinvar id is 1297762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN2	NM_080732.4	c.-234-12del		intron_variant		ENST00000303961.9
RAB4B-EGLN2	NR_037791.1	n.815-12del		intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4	c.-234-12del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN2	ENST00000303961.9	c.-234-12del		intron_variant		1	NM_080732.4	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 36990 AN: 148046 Hom.: 6431 Cov.: 21

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.0348

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.224 AC: 52992 AN: 236118 Hom.: 2380 Cov.: 0 AF XY: 0.223 AC XY: 27204 AN XY: 121910

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.250 AC: 37059 AN: 148128 Hom.: 6458 Cov.: 21 AF XY: 0.246 AC XY: 17787 AN XY: 72176

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0850

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.224

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

Aug 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35057638; hg19: chr19-41306221;