17-2042763-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080822.3(OVCA2):​c.343C>T​(p.Leu115Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000846 in 1,608,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

OVCA2
NM_080822.3 missense

Scores

5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05810225).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OVCA2NM_080822.3 linkuse as main transcriptc.343C>T p.Leu115Phe missense_variant 2/2 ENST00000572195.3 NP_543012.1
DPH1NM_001383.6 linkuse as main transcriptc.*177C>T 3_prime_UTR_variant 13/13 ENST00000263083.12 NP_001374.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OVCA2ENST00000572195.3 linkuse as main transcriptc.343C>T p.Leu115Phe missense_variant 2/21 NM_080822.3 ENSP00000461388 P1
DPH1ENST00000263083.12 linkuse as main transcriptc.*177C>T 3_prime_UTR_variant 13/131 NM_001383.6 ENSP00000263083 P1Q9BZG8-4

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00118
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:
0.00
GnomAD3 exomes
AF:
0.0000780
AC:
19
AN:
243710
Hom.:
0
AF XY:
0.0000453
AC XY:
6
AN XY:
132394
show subpopulations
Gnomad AFR exome
AF:
0.00112
Gnomad AMR exome
AF:
0.0000298
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000598
AC:
87
AN:
1455800
Hom.:
0
Cov.:
32
AF XY:
0.0000497
AC XY:
36
AN XY:
724262
show subpopulations
Gnomad4 AFR exome
AF:
0.00106
Gnomad4 AMR exome
AF:
0.0000230
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000406
Gnomad4 OTH exome
AF:
0.0000999
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00118
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000124
Hom.:
0
Bravo
AF:
0.000393
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000148
AC:
18
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2022The c.343C>T (p.L115F) alteration is located in exon 2 (coding exon 2) of the OVCA2 gene. This alteration results from a C to T substitution at nucleotide position 343, causing the leucine (L) at amino acid position 115 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.54
T
Sift4G
Uncertain
0.020
D
Polyphen
0.86
P
Vest4
0.29
MVP
0.49
MPC
0.031
ClinPred
0.090
T
GERP RS
3.2
Varity_R
0.26
gMVP
0.57

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.

Other links and lift over

dbSNP: rs138550949; hg19: chr17-1946057; API