NM_198185.7:c.1485T>A

Variant names:

• chr11-7691924-A-T
• rs903723635
• NM_198185.7:c.1485T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198185.7(OVCH2):​c.1485T>A​(p.Asp495Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 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: 7.0e-7 (0 hom.)
• Consequence: OVCH2 NM_198185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.984

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30517542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVCH2	NM_198185.7	c.1485T>A	p.Asp495Glu	missense_variant	Exon 13 of 16	ENST00000533663.6	NP_937828.3
OVCH2	XM_047426878.1	c.1497T>A	p.Asp499Glu	missense_variant	Exon 13 of 18		XP_047282834.1
LOC105376533	XR_007062576.1	n.381-57A>T		intron_variant	Intron 3 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVCH2	ENST00000533663.6	c.1485T>A	p.Asp495Glu	missense_variant	Exon 13 of 16	5	NM_198185.7	ENSP00000484497.2
OVCH2	ENST00000612000.1	c.1485T>A	p.Asp495Glu	missense_variant	Exon 13 of 15	5		ENSP00000484790.1
OVCH2	ENST00000673880.1	c.1038T>A	p.Asp346Glu	missense_variant	Exon 9 of 12			ENSP00000501258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420134 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702110

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1485T>A (p.D495E) alteration is located in exon 14 (coding exon 14) of the OVCH2 gene. This alteration results from a T to A substitution at nucleotide position 1485, causing the aspartic acid (D) at amino acid position 495 to be replaced by a glutamic acid (E). 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	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.44	T
Sift4G	Uncertain	0.0020	D;D
Vest4		0.42
MutPred		0.66		Gain of methylation at K499 (P = 0.1126);Gain of methylation at K499 (P = 0.1126);
MVP		0.19
ClinPred		0.98	D
GERP RS		0.061
gMVP		0.44

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: rs903723635; hg19: chr11-7713155;