NM_198185.7:c.1361A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198185.7(OVCH2):​c.1361A>G​(p.Asp454Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,552,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

OVCH2
NM_198185.7 missense

Scores

1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07
Variant links:
Genes affected
OVCH2 (HGNC:29970): (ovochymase 2) Predicted to enable metal ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.075983256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OVCH2NM_198185.7 linkc.1361A>G p.Asp454Gly missense_variant Exon 12 of 16 ENST00000533663.6 NP_937828.3 A0A087X1V8
OVCH2XM_047426878.1 linkc.1373A>G p.Asp458Gly missense_variant Exon 12 of 18 XP_047282834.1
LOC105376533XR_007062576.1 linkn.953+2557T>C intron_variant Intron 4 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OVCH2ENST00000533663.6 linkc.1361A>G p.Asp454Gly missense_variant Exon 12 of 16 5 NM_198185.7 ENSP00000484497.2 A0A087X1V8
OVCH2ENST00000612000.1 linkc.1361A>G p.Asp454Gly missense_variant Exon 12 of 15 5 ENSP00000484790.1 A0A087X1V8
OVCH2ENST00000673880.1 linkc.914A>G p.Asp305Gly missense_variant Exon 8 of 12 ENSP00000501258.1 A0A669KBI9

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD4 exome
AF:
7.14e-7
AC:
1
AN:
1400518
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
690872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.26e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
30
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1361A>G (p.D454G) alteration is located in exon 13 (coding exon 13) of the OVCH2 gene. This alteration results from a A to G substitution at nucleotide position 1361, causing the aspartic acid (D) at amino acid position 454 to be replaced by a glycine (G). 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
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.67
.;T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.30
T
Sift4G
Uncertain
0.015
D;D
Vest4
0.17
MutPred
0.53
Gain of glycosylation at S453 (P = 0.0242);Gain of glycosylation at S453 (P = 0.0242);
MVP
0.18
ClinPred
0.23
T
GERP RS
4.4
gMVP
0.40

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: rs1748457989; hg19: chr11-7716341; API