Variant 19-40800329-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_080732.4(EGLN2):c.-234-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 468,440 control chromosomes in the GnomAD database, including 1,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.073 ( 541 hom., cov: 31)

Exomes 𝑓: 0.059 ( 1156 hom. )

Consequence

EGLN2
NM_080732.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003486

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.253

Variant links:

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]

EGLN2 links:

RAB4B-EGLN2 (HGNC:):

RAB4B-EGLN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-40800329-C-T is Benign according to our data. Variant chr19-40800329-C-T is described in ClinVar as [Benign]. Clinvar id is 1182618.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
EGLN2	NM_080732.4 linkuse as main transcript	c.-234-10C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000303961.9
RAB4B-EGLN2	NR_037791.1 linkuse as main transcript	n.815-10C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4 linkuse as main transcript	c.-234-10C>T	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN2	ENST00000303961.9 linkuse as main transcript	c.-234-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_080732.4	P1	Q96KS0-1

Frequencies

GnomAD3 genomes

AF:

0.0733

AC:

10973

AN:

149632

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.0512

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0591

GnomAD4 exome

AF:

0.0593

AC:

18893

AN:

318692

Hom.:

1156

Cov.:

AF XY:

0.0571

AC XY:

9336

AN XY:

163368

show subpopulations

Gnomad4 AFR exome

AF:

0.0989

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0645

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.0863

Gnomad4 NFE exome

AF:

0.0377

Gnomad4 OTH exome

AF:

0.0578

GnomAD4 genome

AF:

0.0733

AC:

10983

AN:

149748

Hom.:

541

Cov.:

AF XY:

0.0765

AC XY:

5587

AN XY:

73074

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0336

Gnomad4 ASJ

AF:

0.0620

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.0451

Gnomad4 OTH

AF:

0.0580

Alfa

AF:

0.0552

Hom.:

Bravo

AF:

0.0719

Asia WGS

AF:

0.148

AC:

512

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over