19-40799835-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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, single submitter B:1
• Conservation: PhyloP100: 0.544

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 -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN2	NM_080732.4	c.-234-504A>G		intron_variant		ENST00000303961.9
RAB4B-EGLN2	NR_037791.1	n.815-504A>G		intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4	c.-235+197A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44405 AN: 149670 Hom.: 7524 Cov.: 28

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.: 16 Cov.: 0 AF XY: 0.281 AC XY: 77 AN XY: 274

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.: 28 AF XY: 0.295 AC XY: 21505 AN XY: 72958

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs11881124; hg19: chr19-41305740;