19-9854407-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058164.4(OLFM2):​c.1144G>A​(p.Val382Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

OLFM2
NM_058164.4 missense

Scores

7
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76
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]

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OLFM2NM_058164.4 linkc.1144G>A p.Val382Met missense_variant Exon 6 of 6 ENST00000264833.9 NP_477512.1 O95897
OLFM2NM_001304347.2 linkc.1216G>A p.Val406Met missense_variant Exon 6 of 6 NP_001291276.1 O95897K7EKW2
OLFM2NM_001304348.2 linkc.910G>A p.Val304Met missense_variant Exon 5 of 5 NP_001291277.1 O95897K7EIS8
OLFM2XM_047439713.1 linkc.940G>A p.Val314Met missense_variant Exon 6 of 6 XP_047295669.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OLFM2ENST00000264833.9 linkc.1144G>A p.Val382Met missense_variant Exon 6 of 6 1 NM_058164.4 ENSP00000264833.3 O95897
OLFM2ENST00000593091.2 linkc.1216G>A p.Val406Met missense_variant Exon 6 of 6 5 ENSP00000465809.2 K7EKW2
OLFM2ENST00000590841.5 linkc.910G>A p.Val304Met missense_variant Exon 5 of 5 2 ENSP00000464877.1 K7EIS8
OLFM2ENST00000592448.1 linkn.*549G>A downstream_gene_variant 3 ENSP00000466018.1 K7ELC6

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251462
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461882
Hom.:
0
Cov.:
34
AF XY:
0.0000193
AC XY:
14
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1144G>A (p.V382M) alteration is located in exon 6 (coding exon 6) of the OLFM2 gene. This alteration results from a G to A substitution at nucleotide position 1144, causing the valine (V) at amino acid position 382 to be replaced by a methionine (M). 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
0.67
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Pathogenic
0.90
D
MutationAssessor
Pathogenic
3.2
M;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-2.3
N;.
REVEL
Pathogenic
0.76
Sift
Uncertain
0.0040
D;.
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;.
Vest4
0.68
MVP
0.68
MPC
1.8
ClinPred
0.95
D
GERP RS
4.4
Varity_R
0.33

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.

Other links and lift over

dbSNP: rs148943256; hg19: chr19-9965083; API