rs10416308

Positions:

• chr19-40806356-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080732.4(EGLN2):​c.844-199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,074,208 control chromosomes in the GnomAD database, including 18,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5090 hom., cov: 32)
  • Exomes 𝑓: 0.16 (12942 hom.)
• Consequence: EGLN2 NM_080732.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.151

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-40806356-G-A is Benign according to our data. Variant chr19-40806356-G-A is described in ClinVar as [Benign]. Clinvar id is 1260751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.844-199G>A		intron_variant		ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1	n.1892-199G>A		intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4	c.844-199G>A		intron_variant			NP_444274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.844-199G>A		intron_variant		1	NM_080732.4	ENSP00000307080	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34253 AN: 151864 Hom.: 5071 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.160 AC: 147707 AN: 922224 Hom.: 12942 Cov.: 12 AF XY: 0.160 AC XY: 72989 AN XY: 456328

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.226 AC: 34315 AN: 151984 Hom.: 5090 Cov.: 32 AF XY: 0.222 AC XY: 16490 AN XY: 74308

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.208

Alfa AF: 0.207 Hom.: 474

Bravo AF: 0.237

Asia WGS AF: 0.142 AC: 496 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.64
CADD	Benign	7.8
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10416308; hg19: chr19-41312261;