chr11-7691360-G-T

Position:

• chr11-7691360-G-T

Variant summary

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

The NM_198185.7(OVCH2):​c.1548C>A​(p.Ser516Arg) variant causes a missense change involving the alteration of a non-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: 2.27

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, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OVCH2	NM_198185.7	c.1548C>A	p.Ser516Arg	missense_variant	14/16	ENST00000533663.6
LOC105376533	XR_007062576.1	n.248G>T		non_coding_transcript_exon_variant	3/11
OVCH2	XM_047426878.1	c.1560C>A	p.Ser520Arg	missense_variant	14/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OVCH2	ENST00000533663.6	c.1548C>A	p.Ser516Arg	missense_variant	14/16	5	NM_198185.7	P1
OVCH2	ENST00000612000.1	c.1548C>A	p.Ser516Arg	missense_variant	14/15	5		P1
OVCH2	ENST00000673880.1	c.1104C>A	p.Ser368Arg	missense_variant	10/12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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 29, 2023

The c.1548C>A (p.S516R) 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 1548, causing the serine (S) at amino acid position 516 to be replaced by an arginine (R). 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	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.50	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.71
MutPred		0.86		Gain of catalytic residue at S516 (P = 0.0763);Gain of catalytic residue at S516 (P = 0.0763);
MVP		0.12
ClinPred		0.97	D
GERP RS		3.7
gMVP		0.85

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: chr11-7712591;