19-40799342-T-TG

Position:

• chr19-40799342-T-TG

Variant summary

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

The NM_080732.4(EGLN2):​c.-235+85dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (3921 hom., cov: 19)
  • Exomes 𝑓: 0.091 (1 hom.)
• Consequence: EGLN2 NM_080732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

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 19-40799342-T-TG is Benign according to our data. Variant chr19-40799342-T-TG is described in ClinVar as [Benign]. Clinvar id is 1260928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.-235+85dup		intron_variant		ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1	n.815-992dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.-235+85dup		intron_variant		1	NM_080732.4	ENSP00000307080	P1
EGLN2	ENST00000598654.1	c.-235+299dup		intron_variant		3		ENSP00000471568

Frequencies

GnomAD3 genomes AF: 0.241 AC: 30369 AN: 125806 Hom.: 3902 Cov.: 19

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0389

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.0909 AC: 4 AN: 44 Hom.: 1 Cov.: 0 AF XY: 0.133 AC XY: 4 AN XY: 30

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0952

GnomAD4 genome AF: 0.242 AC: 30428 AN: 125914 Hom.: 3921 Cov.: 19 AF XY: 0.241 AC XY: 14685 AN XY: 60990

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.237

Alfa AF: 0.193 Hom.: 200

Asia WGS AF: 0.122 AC: 388 AN: 3190

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

Oct 03, 2018

- -

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: rs376020782; hg19: chr19-41305247;