ENST00000601627.1:n.118-235C>A

Variant names:

• chr19-40801179-G-A
• NM_080732.4:c.607G>A

Variant summary

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

The NM_080732.4(EGLN2):​c.607G>A​(p.Gly203Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EGLN2 NM_080732.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.00

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.607G>A	p.Gly203Ser	missense_variant	Exon 2 of 6	ENST00000303961.9	NP_542770.2
EGLN2	NM_053046.4	c.607G>A	p.Gly203Ser	missense_variant	Exon 2 of 6		NP_444274.1
RAB4B-EGLN2	NR_037791.1	n.1655G>A		non_coding_transcript_exon_variant	Exon 8 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.607G>A	p.Gly203Ser	missense_variant	Exon 2 of 6	1	NM_080732.4	ENSP00000307080.3
RAB4B-EGLN2	ENST00000594136.2	n.*856G>A		non_coding_transcript_exon_variant	Exon 8 of 12	2		ENSP00000469872.1
RAB4B-EGLN2	ENST00000594136.2	n.*856G>A		3_prime_UTR_variant	Exon 8 of 12	2		ENSP00000469872.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D;D
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	.;.;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.6	D;D;.
REVEL	Benign	0.21
Sift	Benign	0.031	D;D;.
Sift4G	Uncertain	0.029	D;D;D
Polyphen		0.78	P;P;P
Vest4		0.61
MutPred		0.55		Gain of phosphorylation at G203 (P = 0.0711);Gain of phosphorylation at G203 (P = 0.0711);Gain of phosphorylation at G203 (P = 0.0711);
MVP		0.69
MPC		1.3
ClinPred		0.97	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.57
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr19-41307084;