Variant chr17-2042327-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000571710.6(DPH1):c.*470G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,373,446 control chromosomes in the GnomAD database, including 363,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40254 hom., cov: 26)

Exomes 𝑓: 0.73 ( 322972 hom. )

Consequence

DPH1
ENST00000571710.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.643

Variant links:

Genes affected

DPH1 (HGNC:3003): (diphthamide biosynthesis 1) The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas exotoxin A. Defects in this gene have been associated with both ovarian cancer and autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. [provided by RefSeq, Oct 2016]

DPH1 links:

OVCA2 (HGNC:24203): (OVCA2 serine hydrolase domain containing) Involved in response to retinoic acid. Located in cytoplasm. Biomarker of ovarian cancer. [provided by Alliance of Genome Resources, Apr 2022]

OVCA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-2042327-G-T is Benign according to our data. Variant chr17-2042327-G-T is described in ClinVar as [Benign]. Clinvar id is 1302072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPH1	NM_001383.6 linkuse as main transcript	c.*19-278G>T		intron_variant		ENST00000263083.12
OVCA2	NM_080822.3 linkuse as main transcript	c.184+96G>T		intron_variant		ENST00000572195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPH1	ENST00000263083.12 linkuse as main transcript	c.*19-278G>T		intron_variant		1	NM_001383.6	P1	Q9BZG8-4
OVCA2	ENST00000572195.3 linkuse as main transcript	c.184+96G>T		intron_variant		1	NM_080822.3	P1

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110098

AN:

150816

Hom.:

40220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.801

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.737

GnomAD4 exome

AF:

0.726

AC:

887296

AN:

1222512

Hom.:

322972

Cov.:

AF XY:

0.724

AC XY:

427940

AN XY:

590860

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.836

Gnomad4 ASJ exome

AF:

0.769

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.743

Gnomad4 NFE exome

AF:

0.723

Gnomad4 OTH exome

AF:

0.737

GnomAD4 genome

AF:

0.730

AC:

110185

AN:

150934

Hom.:

40254

Cov.:

AF XY:

0.730

AC XY:

53743

AN XY:

73666

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.802

Gnomad4 ASJ

AF:

0.762

Gnomad4 EAS

AF:

0.832

Gnomad4 SAS

AF:

0.663

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.722

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.727

Hom.:

4841

Bravo

AF:

0.735

Asia WGS

AF:

0.754

AC:

2620

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.81

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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