rs542447178

Variant names:

• chr11-7696584-C-A
• rs542447178
• NM_198185.7:c.1022G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-7696584-C-A
• chr11-7696584-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_198185.7(OVCH2):​c.1022G>T​(p.Cys341Phe) 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. C341Y) 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: 3.36
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

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.1022G>T	p.Cys341Phe	missense	Exon 10 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.1022G>T	p.Cys341Phe	missense	Exon 10 of 16	ENSP00000484497.2	A0A087X1V8
	OVCH2	ENST00000612000.1	TSL:5	c.1022G>T	p.Cys341Phe	missense	Exon 10 of 15	ENSP00000484790.1	A0A087X1V8
	OVCH2	ENST00000673880.1		c.836-1396G>T		intron	N/A	ENSP00000501258.1	A0A669KBI9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.19	D
PhyloP100		3.4
PrimateAI	Uncertain	0.53	T
Sift4G	Pathogenic	0.0	D
Vest4		0.69
MutPred		0.88		Loss of catalytic residue at K338 (P = 0.0708)
MVP		0.088
ClinPred		0.99	D
GERP RS		4.4
gMVP		0.92
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs542447178; hg19: chr11-7718131;