Variant 19-9856896-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_058164.4(OLFM2):c.598G>A(p.Gly200Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,610,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

OLFM2
NM_058164.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, OLFM2

BP4

Computational evidence support a benign effect (MetaRNN=0.35936338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFM2	NM_058164.4 linkuse as main transcript	c.598G>A	p.Gly200Arg	missense_variant	5/6	ENST00000264833.9
OLFM2	NM_001304347.2 linkuse as main transcript	c.670G>A	p.Gly224Arg	missense_variant	5/6
OLFM2	NM_001304348.2 linkuse as main transcript	c.364G>A	p.Gly122Arg	missense_variant	4/5
OLFM2	XM_047439713.1 linkuse as main transcript	c.394G>A	p.Gly132Arg	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OLFM2	ENST00000264833.9 linkuse as main transcript	c.598G>A	p.Gly200Arg	missense_variant	5/6	1	NM_058164.4
OLFM2	ENST00000593091.2 linkuse as main transcript	c.670G>A	p.Gly224Arg	missense_variant	5/6	5		P1
OLFM2	ENST00000590841.5 linkuse as main transcript	c.364G>A	p.Gly122Arg	missense_variant	4/5	2
OLFM2	ENST00000592448.1 linkuse as main transcript	c.*3G>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

240888

Hom.:

AF XY:

0.0000383

AC XY:

AN XY:

130644

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1457868

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

724812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000811

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.000151

ExAC

AF:

0.0000247

AC:

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

Feb 15, 2023

The c.598G>A (p.G200R) alteration is located in exon 5 (coding exon 5) of the OLFM2 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the glycine (G) at amino acid position 200 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

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

T;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.2

D;.;.

REVEL

Uncertain

0.50

Sift

Benign

0.14

T;.;.

Sift4G

Uncertain

0.015

D;D;.

Polyphen

0.99

D;.;.

Vest4

0.75

MutPred

0.42

Gain of MoRF binding (P = 0.0064);.;.;

MVP

0.19

MPC

1.7

ClinPred

0.36

GERP RS

4.3

Varity_R

0.31

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

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