GeneBe

19-40800316-CTTTTTT-CTTTTTTT

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The ENST00000593726(EGLN2):​c.-246dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 390,398 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: 𝑓 0.00017 ( 0 hom., cov: 21)
Exomes 𝑓: 0.035 ( 0 hom. )

Consequence

EGLN2
ENST00000593726 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.329
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0353 (8540/242106) while in subpopulation MID AF= 0.0443 (48/1084). AF 95% confidence interval is 0.0362. There are 0 homozygotes in gnomad4_exome. There are 4397 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EGLN2NM_080732.4 linkc.-234-12dupT intron_variant Intron 1 of 5 ENST00000303961.9 NP_542770.2 Q96KS0-1A0A024R0R2
EGLN2NM_053046.4 linkc.-234-12dupT intron_variant Intron 1 of 5 NP_444274.1 Q96KS0-1A0A024R0R2
RAB4B-EGLN2NR_037791.1 linkn.815-12dupT intron_variant Intron 7 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EGLN2ENST00000303961.9 linkc.-234-12dupT intron_variant Intron 1 of 5 1 NM_080732.4 ENSP00000307080.3 Q96KS0-1
RAB4B-EGLN2ENST00000594136.2 linkn.*16-12dupT intron_variant Intron 7 of 11 2 ENSP00000469872.1

Frequencies

GnomAD3 genomes
AF:
0.000169
AC:
25
AN:
148210
Hom.:
0
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.0000248
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000268
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000394
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000616
Gnomad MID
AF:
0.00321
Gnomad NFE
AF:
0.000165
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0353
AC:
8540
AN:
242106
Hom.:
0
Cov.:
0
AF XY:
0.0352
AC XY:
4397
AN XY:
124890
show subpopulations
Gnomad4 AFR exome
AF:
0.0116
Gnomad4 AMR exome
AF:
0.0349
Gnomad4 ASJ exome
AF:
0.0388
Gnomad4 EAS exome
AF:
0.0365
Gnomad4 SAS exome
AF:
0.0304
Gnomad4 FIN exome
AF:
0.0342
Gnomad4 NFE exome
AF:
0.0370
Gnomad4 OTH exome
AF:
0.0335
GnomAD4 genome
AF:
0.000169
AC:
25
AN:
148292
Hom.:
0
Cov.:
21
AF XY:
0.000138
AC XY:
10
AN XY:
72264
show subpopulations
Gnomad4 AFR
AF:
0.0000247
Gnomad4 AMR
AF:
0.000268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000395
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000616
Gnomad4 NFE
AF:
0.000165
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35057638; hg19: chr19-41306221; API