Genetic Variant NM_080822.3:c.6C>A (chr17-2042053-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_080822.3(OVCA2):c.6C>A(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,529,252 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0026 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 288 hom. )

Consequence

OVCA2
NM_080822.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

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:

ENSG00000287553 (HGNC:):

ENSG00000287553 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVCA2	NM_080822.3 link	c.6C>A	p.Ala2Ala	synonymous_variant	Exon 1 of 2	ENST00000572195.3	NP_543012.1	Q8WZ82
DPH1	NM_001383.6 link	c.*18+178C>A		intron_variant	Intron 12 of 12	ENST00000263083.12	NP_001374.4	Q9BZG8-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVCA2	ENST00000572195.3 link	c.6C>A	p.Ala2Ala	synonymous_variant	Exon 1 of 2	1	NM_080822.3	ENSP00000461388.1		Q8WZ82
DPH1	ENST00000263083.12 link	c.*18+178C>A		intron_variant	Intron 12 of 12	1	NM_001383.6	ENSP00000263083.7		Q9BZG8-4

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

399

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0793

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0124

AC:

1694

AN:

136118

Hom.:

AF XY:

0.0161

AC XY:

1239

AN XY:

76802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00447

AC:

6158

AN:

1376926

Hom.:

288

Cov.:

AF XY:

0.00659

AC XY:

4479

AN XY:

680042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000995

Gnomad4 AMR exome

AF:

0.000207

Gnomad4 ASJ exome

AF:

0.0000415

Gnomad4 EAS exome

AF:

0.0000557

Gnomad4 SAS exome

AF:

0.0732

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00424

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152326

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0795

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000433

Hom.:

Bravo

AF:

0.000499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.20

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over