19-40799342-T-TG

Variant names:

• chr19-40799342-T-TG
• rs376020782
• NM_080732.4:c.-235+85dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_080732.4(EGLN2):​c.-235+85dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (3921 hom., cov: 19)
  • Exomes 𝑓: 0.091 (1 hom.)
• Consequence: EGLN2 NM_080732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-40799342-T-TG is Benign according to our data. Variant chr19-40799342-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1260928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

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.-235+85dupG		intron	N/A	NP_542770.2	Q96KS0-1
	RAB4B-EGLN2	NR_037791.1		n.815-992dupG		intron	N/A
	EGLN2	NM_053046.4		c.-531_-530insG		upstream_gene	N/A	NP_444274.1	Q96KS0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.-235+85dupG		intron	N/A	ENSP00000307080.3	Q96KS0-1
	RAB4B-EGLN2	ENST00000594136.2	TSL:2	n.*16-992dupG		intron	N/A	ENSP00000469872.1
	EGLN2	ENST00000936252.1		c.-280dupG		5_prime_UTR	Exon 1 of 6	ENSP00000606311.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 30369 AN: 125806 Hom.: 3902 Cov.: 19

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0389

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.0909 AC: 4 AN: 44 Hom.: 1 Cov.: 0 AF XY: 0.133 AC XY: 4 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0952 AC: 4 AN: 42

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.242 AC: 30428 AN: 125914 Hom.: 3921 Cov.: 19 AF XY: 0.241 AC XY: 14685 AN XY: 60990

African (AFR) AF: 0.394 AC: 13913 AN: 35282

American (AMR) AF: 0.221 AC: 2791 AN: 12626

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 501 AN: 3048

East Asian (EAS) AF: 0.0961 AC: 373 AN: 3880

South Asian (SAS) AF: 0.241 AC: 884 AN: 3672

European-Finnish (FIN) AF: 0.169 AC: 1256 AN: 7412

Middle Eastern (MID) AF: 0.211 AC: 51 AN: 242

European-Non Finnish (NFE) AF: 0.178 AC: 10227 AN: 57350

Other (OTH) AF: 0.237 AC: 405 AN: 1708

Alfa AF: 0.193 Hom.: 200

Asia WGS AF: 0.122 AC: 388 AN: 3190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs376020782; hg19: chr19-41305247;