11-7691358-G-T

Position:

• chr11-7691358-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198185.7(OVCH2):​c.1550C>A​(p.Pro517His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,626 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: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: OVCH2 NM_198185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331

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 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=0.097742766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVCH2	NM_198185.7	c.1550C>A	p.Pro517His	missense_variant	14/16	ENST00000533663.6	NP_937828.3
LOC105376533	XR_007062576.1	n.246G>T		non_coding_transcript_exon_variant	3/11
OVCH2	XM_047426878.1	c.1562C>A	p.Pro521His	missense_variant	14/18		XP_047282834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVCH2	ENST00000533663.6	c.1550C>A	p.Pro517His	missense_variant	14/16	5	NM_198185.7	ENSP00000484497	P1
OVCH2	ENST00000612000.1	c.1550C>A	p.Pro517His	missense_variant	14/15	5		ENSP00000484790	P1
OVCH2	ENST00000673880.1	c.1106C>A	p.Pro369His	missense_variant	10/12			ENSP00000501258

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461626 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727096

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

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

Nov 17, 2023

The c.1550C>A (p.P517H) alteration is located in exon 15 (coding exon 15) of the OVCH2 gene. This alteration results from a C to A substitution at nucleotide position 1550, causing the proline (P) at amino acid position 517 to be replaced by a histidine (H). 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	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.76
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
Sift4G	Uncertain	0.021	D;D
Vest4		0.17
MutPred		0.47		Gain of catalytic residue at P517 (P = 0.0112);Gain of catalytic residue at P517 (P = 0.0112);
MVP		0.081
ClinPred		0.38	T
GERP RS		0.14
gMVP		0.22

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

Other links and lift over

dbSNP: rs1856216302; hg19: chr11-7712589;