chr19-40800316-C-CT

Variant names:

• chr19-40800316-C-CT
• rs35057638
• ENST00000593726:c.-246dupT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

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 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
EGLN2	NM_080732.4	c.-234-12dupT		intron_variant	Intron 1 of 5	ENST00000303961.9	NP_542770.2
EGLN2	NM_053046.4	c.-234-12dupT		intron_variant	Intron 1 of 5		NP_444274.1
RAB4B-EGLN2	NR_037791.1	n.815-12dupT		intron_variant	Intron 7 of 11

Ensembl

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

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

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

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

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: rs35057638; hg19: chr19-41306221;