rs137977848

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_080822.3(OVCA2):c.281G>A(p.Gly94Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,550,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G94R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

OVCA2
NM_080822.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

developmental delay with short stature, dysmorphic facial features, and sparse hair
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet
developmental delay with short stature, dysmorphic facial features, and sparse hair 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

DPH1 links:

ENSG00000262533 (HGNC:):

ENSG00000262533 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080822.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OVCA2	NM_080822.3	MANE Select	c.281G>A	p.Gly94Asp	missense	Exon 2 of 2	NP_543012.1	Q8WZ82
DPH1	NM_001383.6	MANE Select	c.*115G>A		3_prime_UTR	Exon 13 of 13	NP_001374.4	Q9BZG8-4
DPH1	NM_001346574.1		c.*115G>A		3_prime_UTR	Exon 13 of 13	NP_001333503.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OVCA2	ENST00000572195.3	TSL:1 MANE Select	c.281G>A	p.Gly94Asp	missense	Exon 2 of 2	ENSP00000461388.1	Q8WZ82
DPH1	ENST00000263083.12	TSL:1 MANE Select	c.*115G>A		3_prime_UTR	Exon 13 of 13	ENSP00000263083.7	Q9BZG8-4
DPH1	ENST00000571710.6	TSL:1	c.*844G>A		3_prime_UTR	Exon 5 of 5	ENSP00000460813.1	I3L3X9

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000714

AC:

AN:

196008

AF XY:

0.0000382

show subpopulations

Gnomad AFR exome

AF:

0.000835

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000220

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1397912

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

689704

show subpopulations

African (AFR)

AF:

0.000741

AC:

AN:

31032

American (AMR)

AF:

0.00

AC:

AN:

33642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21608

East Asian (EAS)

AF:

0.00

AC:

AN:

39256

South Asian (SAS)

AF:

0.00

AC:

AN:

75154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1083644

Other (OTH)

AF:

0.0000348

AC:

AN:

57518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000295

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000160

Hom.:

Bravo

AF:

0.000298

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000990

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.11

PhyloP100

7.8

PrimateAI

Uncertain

0.69

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.89

MVP

0.61

MPC

0.22

ClinPred

0.45

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

gMVP

0.80

Mutation Taster

=16/84

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over