chr19-40800316-CTTT-C

Variant names:

• chr19-40800316-CTTT-C
• ENST00000593726:c.-248_-246delTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000593726(EGLN2):​c.-248_-246delTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 251,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: EGLN2 ENST00000593726 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

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:44465): (RAB4B-EGLN2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RAB4B (RAB4B, member RAS oncogene family) and EGLN2 (egl nine homolog 2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.-234-14_-234-12delTTT		intron_variant	Intron 1 of 5	ENST00000303961.9	NP_542770.2
EGLN2	NM_053046.4	c.-234-14_-234-12delTTT		intron_variant	Intron 1 of 5		NP_444274.1
RAB4B-EGLN2	NR_037791.1	n.815-14_815-12delTTT		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.-234-14_-234-12delTTT		intron_variant	Intron 1 of 5	1	NM_080732.4	ENSP00000307080.3
RAB4B-EGLN2	ENST00000594136.2	n.*16-14_*16-12delTTT		intron_variant	Intron 7 of 11	2		ENSP00000469872.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.0000159 AC: 4 AN: 251022 Hom.: 0 AF XY: 0.0000309 AC XY: 4 AN XY: 129578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000598

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-41306221;