19-40800457-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_080732.4(EGLN2):c.-116G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,425,032 control chromosomes in the GnomAD database, including 88,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7791 hom., cov: 32)
  • Exomes 𝑓: 0.35 (80640 hom.)
• Consequence: EGLN2 NM_080732.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.534

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-40800457-G-A is Benign according to our data. Variant chr19-40800457-G-A is described in ClinVar as [Benign]. Clinvar id is 1283246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN2	NM_080732.4	c.-116G>A		5_prime_UTR_variant	2/6	ENST00000303961.9
RAB4B-EGLN2	NR_037791.1	n.933G>A		non_coding_transcript_exon_variant	8/12
EGLN2	NM_053046.4	c.-116G>A		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN2	ENST00000303961.9	c.-116G>A		5_prime_UTR_variant	2/6	1	NM_080732.4	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43464 AN: 151830 Hom.: 7784 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.351 AC: 447178 AN: 1273084 Hom.: 80640 Cov.: 25 AF XY: 0.353 AC XY: 218371 AN XY: 618942

Gnomad4 AFR exome AF: 0.0569

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.359

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.286 AC: 43482 AN: 151948 Hom.: 7791 Cov.: 32 AF XY: 0.289 AC XY: 21490 AN XY: 74286

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.321

Alfa AF: 0.291 Hom.: 918

Bravo AF: 0.282

Asia WGS AF: 0.395 AC: 1372 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	8.6
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11547373; hg19: chr19-41306362; COSMIC: COSV58279323; COSMIC: COSV58279323;