11-7691397-C-G

Variant names:

• chr11-7691397-C-G
• rs770799975
• NM_198185.7:c.1511G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198185.7(OVCH2):​c.1511G>C​(p.Arg504Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R504Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OVCH2 NM_198185.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198185.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVCH2	NM_198185.7	MANE Select	c.1511G>C	p.Arg504Pro	missense	Exon 14 of 16	NP_937828.3	A0A087X1V8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVCH2	ENST00000533663.6	TSL:5 MANE Select	c.1511G>C	p.Arg504Pro	missense	Exon 14 of 16	ENSP00000484497.2	A0A087X1V8
	OVCH2	ENST00000612000.1	TSL:5	c.1511G>C	p.Arg504Pro	missense	Exon 14 of 15	ENSP00000484790.1	A0A087X1V8
	OVCH2	ENST00000673880.1		c.1064G>C	p.Arg355Pro	missense	Exon 10 of 12	ENSP00000501258.1	A0A669KBI9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.89	T
PhyloP100		0.61
PrimateAI	Benign	0.27	T
Sift4G	Uncertain	0.0020	D
Vest4		0.57
MutPred		0.69		Gain of methylation at K500 (P = 0.0372)
MVP		0.055
ClinPred		0.95	D
GERP RS		5.6
gMVP		0.80
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs770799975; hg19: chr11-7712628;