19-40800578-C-G

Variant names:

• chr19-40800578-C-G
• rs775547797
• NM_080732.4:c.6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_080732.4(EGLN2):​c.6C>G​(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,444,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: EGLN2 NM_080732.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2549954).

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.6C>G	p.Asp2Glu	missense	Exon 2 of 6	NP_542770.2	Q96KS0-1
	EGLN2	NM_053046.4		c.6C>G	p.Asp2Glu	missense	Exon 2 of 6	NP_444274.1	Q96KS0-1
	RAB4B-EGLN2	NR_037791.1		n.1054C>G		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.6C>G	p.Asp2Glu	missense	Exon 2 of 6	ENSP00000307080.3	Q96KS0-1
	EGLN2	ENST00000406058.6	TSL:1	c.6C>G	p.Asp2Glu	missense	Exon 2 of 6	ENSP00000385253.1	Q96KS0-1
	EGLN2	ENST00000593726.5	TSL:1	c.6C>G	p.Asp2Glu	missense	Exon 1 of 5	ENSP00000469686.1	Q96KS0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000603 AC: 14 AN: 232116 AF XY: 0.0000396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000421

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 16 AN: 1444052 Hom.: 1 Cov.: 32 AF XY: 0.00000698 AC XY: 5 AN XY: 716292

African (AFR) AF: 0.00 AC: 0 AN: 33226

American (AMR) AF: 0.000366 AC: 16 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25302

East Asian (EAS) AF: 0.00 AC: 0 AN: 39258

South Asian (SAS) AF: 0.00 AC: 0 AN: 84456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5046

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102710

Other (OTH) AF: 0.00 AC: 0 AN: 59466

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.48
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.11
MutPred		0.19		Gain of glycosylation at P4 (P = 0.0696)
MVP		0.63
MPC		0.52
ClinPred		0.24	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.16
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs775547797; hg19: chr19-41306483;