19-40800583-CG-TA

Variant names:

• chr19-40800583-CG-TA
• NM_080732.4:c.11_12delCGinsTA
• EGLN2 p.Pro4Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_080732.4(EGLN2):​c.11_12delCGinsTA​(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EGLN2 NM_080732.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080732.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	NM_080732.4	MANE Select	c.11_12delCGinsTA	p.Pro4Leu	missense	N/A	NP_542770.2	Q96KS0-1
	EGLN2	NM_053046.4		c.11_12delCGinsTA	p.Pro4Leu	missense	N/A	NP_444274.1	Q96KS0-1
	RAB4B-EGLN2	NR_037791.1		n.1059_1060delCGinsTA		non_coding_transcript_exon	Exon 8 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.11_12delCGinsTA	p.Pro4Leu	missense	N/A	ENSP00000307080.3	Q96KS0-1
	EGLN2	ENST00000406058.6	TSL:1	c.11_12delCGinsTA	p.Pro4Leu	missense	N/A	ENSP00000385253.1	Q96KS0-1
	EGLN2	ENST00000593726.5	TSL:1	c.11_12delCGinsTA	p.Pro4Leu	missense	N/A	ENSP00000469686.1	Q96KS0-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.95

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-41306488;