11-7702189-G-A

Position:

• chr11-7702189-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_198185.7(OVCH2):​c.431C>T​(p.Ala144Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OVCH2 NM_198185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

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]

LOC105376533 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.976

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OVCH2	NM_198185.7	c.431C>T	p.Ala144Val	missense_variant	4/16	ENST00000533663.6
LOC105376533	XR_007062576.1	n.1117+1082G>A		intron_variant, non_coding_transcript_variant
OVCH2	NM_001367963.1	c.431C>T	p.Ala144Val	missense_variant	4/7
OVCH2	XM_047426878.1	c.443C>T	p.Ala148Val	missense_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OVCH2	ENST00000533663.6	c.431C>T	p.Ala144Val	missense_variant	4/16	5	NM_198185.7	P1
OVCH2	ENST00000612000.1	c.431C>T	p.Ala144Val	missense_variant	4/15	5		P1
OVCH2	ENST00000673880.1	c.344C>T	p.Ala115Val	missense_variant	3/12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.431C>T (p.A144V) alteration is located in exon 4 (coding exon 4) of the OVCH2 gene. This alteration results from a C to T substitution at nucleotide position 431, causing the alanine (A) at amino acid position 144 to be replaced by a valine (V). 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	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	1.0	D
MutationTaster	Benign	0.70	N
PrimateAI	Uncertain	0.56	T
Sift4G	Pathogenic	0.0010	D;D
Vest4		0.77
MutPred		0.92		Gain of catalytic residue at A144 (P = 0.0894);Gain of catalytic residue at A144 (P = 0.0894);
MVP		0.12
ClinPred		0.99	D
GERP RS		5.9
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-7723736;