Variant 11-7695620-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198185.7(OVCH2):c.1232C>G(p.Ala411Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,422 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: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

OVCH2
NM_198185.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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]

OVCH2 links:

LOC105376533 (HGNC:):

LOC105376533 links:

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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=0.06251243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVCH2	NM_198185.7 linkuse as main transcript	c.1232C>G	p.Ala411Gly	missense_variant	11/16	ENST00000533663.6	NP_937828.3	A0A087X1V8
OVCH2	XM_047426878.1 linkuse as main transcript	c.1244C>G	p.Ala415Gly	missense_variant	11/18		XP_047282834.1
LOC105376533	XR_007062576.1 linkuse as main transcript	n.953+3067G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OVCH2	ENST00000533663.6 linkuse as main transcript	c.1232C>G	p.Ala411Gly	missense_variant	11/16	5	NM_198185.7	ENSP00000484497.2	A0A087X1V8
OVCH2	ENST00000612000.1 linkuse as main transcript	c.1232C>G	p.Ala411Gly	missense_variant	11/15	5		ENSP00000484790.1	A0A087X1V8
OVCH2	ENST00000673880.1 linkuse as main transcript	c.836-432C>G		intron_variant				ENSP00000501258.1	A0A669KBI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248982

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000278

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:

0.00000547

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000166

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.1232C>G (p.A411G) alteration is located in exon 12 (coding exon 12) of the OVCH2 gene. This alteration results from a C to G substitution at nucleotide position 1232, causing the alanine (A) at amino acid position 411 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

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.0054

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.36

Sift4G

Benign

1.0

T;T

Vest4

0.15

MutPred

0.59

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.099

ClinPred

0.40

GERP RS

3.7

gMVP

0.31

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.

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