chr19-40799888-CTCTG-C

Position:

• chr19-40799888-CTCTG-C

Variant summary

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

The ENST00000593726.5(EGLN2):​c.-681_-678del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 144,186 control chromosomes in the GnomAD database, including 12,392 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12386 hom., cov: 0)
  • Exomes 𝑓: 0.24 (6 hom.)
• Consequence: EGLN2 ENST00000593726.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.344

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 19-40799888-CTCTG-C is Benign according to our data. Variant chr19-40799888-CTCTG-C is described in ClinVar as [Benign]. Clinvar id is 1228205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.-234-447_-234-444del		intron_variant		ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1	n.815-447_815-444del		intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4	c.-235+254_-235+257del		intron_variant			NP_444274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.-234-447_-234-444del		intron_variant		1	NM_080732.4	ENSP00000307080	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 56586 AN: 143960 Hom.: 12385 Cov.: 0

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.236 AC: 26 AN: 110 Hom.: 6 AF XY: 0.206 AC XY: 14 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.393 AC: 56612 AN: 144076 Hom.: 12386 Cov.: 0 AF XY: 0.391 AC XY: 27198 AN XY: 69556

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.429

Alfa AF: 0.394 Hom.: 1361

Asia WGS AF: 0.512 AC: 1770 AN: 3458

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 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs111833532; hg19: chr19-41305793;