Variant 17-2042053-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_080822.3(OVCA2):c.6C>T(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,529,268 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 16 hom. )

Consequence

OVCA2
NM_080822.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.22

Variant links:

Genes affected

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:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-2042053-C-T is Benign according to our data. Variant chr17-2042053-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067207.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.22 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVCA2	NM_080822.3 linkuse as main transcript	c.6C>T	p.Ala2=	synonymous_variant	1/2	ENST00000572195.3	NP_543012.1
DPH1	NM_001383.6 linkuse as main transcript	c.*18+178C>T		intron_variant		ENST00000263083.12	NP_001374.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVCA2	ENST00000572195.3 linkuse as main transcript	c.6C>T	p.Ala2=	synonymous_variant	1/2	1	NM_080822.3	ENSP00000461388	P1
DPH1	ENST00000263083.12 linkuse as main transcript	c.*18+178C>T		intron_variant		1	NM_001383.6	ENSP00000263083	P1	Q9BZG8-4

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

422

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00464

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00296

AC:

403

AN:

136118

Hom.:

AF XY:

0.00292

AC XY:

224

AN XY:

76802

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00315

Gnomad FIN exome

AF:

0.00138

Gnomad NFE exome

AF:

0.00454

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00358

AC:

4935

AN:

1376940

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

2384

AN XY:

680054

show subpopulations

Gnomad4 AFR exome

AF:

0.000431

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.0000830

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00348

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00406

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00277

AC:

422

AN:

152328

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00387

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00287

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

OVCA2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.28

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

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