Variant chr19-9854854-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_058164.4(OLFM2):c.697A>G(p.Met233Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,439,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OLFM2
NM_058164.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OLFM2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, OLFM2

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFM2	NM_058164.4 linkuse as main transcript	c.697A>G	p.Met233Val	missense_variant	6/6	ENST00000264833.9
OLFM2	NM_001304347.2 linkuse as main transcript	c.769A>G	p.Met257Val	missense_variant	6/6
OLFM2	NM_001304348.2 linkuse as main transcript	c.463A>G	p.Met155Val	missense_variant	5/5
OLFM2	XM_047439713.1 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OLFM2	ENST00000264833.9 linkuse as main transcript	c.697A>G	p.Met233Val	missense_variant	6/6	1	NM_058164.4
OLFM2	ENST00000593091.2 linkuse as main transcript	c.769A>G	p.Met257Val	missense_variant	6/6	5		P1
OLFM2	ENST00000590841.5 linkuse as main transcript	c.463A>G	p.Met155Val	missense_variant	5/5	2
OLFM2	ENST00000592448.1 linkuse as main transcript	c.*102A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000451

AC:

AN:

221686

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1439296

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000706

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.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The c.697A>G (p.M233V) alteration is located in exon 6 (coding exon 6) of the OLFM2 gene. This alteration results from a A to G substitution at nucleotide position 697, causing the methionine (M) at amino acid position 233 to be replaced by a valine (V). 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

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.070

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Uncertain

0.43

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

N;.;.

REVEL

Pathogenic

0.70

Sift

Benign

0.11

T;.;.

Sift4G

Benign

0.14

T;T;.

Polyphen

0.97

D;.;.

Vest4

0.58

MutPred

0.77

Loss of MoRF binding (P = 0.0924);.;.;

MVP

0.30

MPC

0.97

ClinPred

0.67

GERP RS

4.5

Varity_R

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over