chr19-40799402-G-T

Position:

• chr19-40799402-G-T

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.-235+140G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 144,408 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (347 hom., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EGLN2 NM_080732.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0670

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 19-40799402-G-T is Benign according to our data. Variant chr19-40799402-G-T is described in ClinVar as [Benign]. Clinvar id is 1283406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.-235+140G>T		intron_variant		ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1	n.815-937G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.-235+140G>T		intron_variant		1	NM_080732.4	ENSP00000307080	P1
EGLN2	ENST00000598654.1	c.-235+354G>T		intron_variant		3		ENSP00000471568
EGLN2	ENST00000593972.1			upstream_gene_variant		2		ENSP00000471546

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 8679 AN: 144296 Hom.: 345 Cov.: 22

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.0642

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0474

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0602 AC: 8688 AN: 144408 Hom.: 347 Cov.: 22 AF XY: 0.0622 AC XY: 4383 AN XY: 70486

Gnomad4 AFR AF: 0.0818

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.0399

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0520 Hom.: 28

Bravo AF: 0.0627

Asia WGS AF: 0.0930 AC: 312 AN: 3342

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs192477377; hg19: chr19-41305307;