9-124801610-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182487.4(OLFML2A):​c.866G>A​(p.Arg289Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,822 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

OLFML2A
NM_182487.4 missense

Scores

8
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59
Variant links:
Genes affected
OLFML2A (HGNC:27270): (olfactomedin like 2A) Predicted to enable extracellular matrix binding activity and identical protein binding activity. Predicted to act upstream of or within extracellular matrix organization. Predicted to be located in extracellular matrix and extracellular region. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4222133).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OLFML2ANM_182487.4 linkuse as main transcriptc.866G>A p.Arg289Gln missense_variant 5/8 ENST00000373580.8 NP_872293.2 Q68BL7-1
OLFML2ANM_001282715.2 linkuse as main transcriptc.224G>A p.Arg75Gln missense_variant 2/5 NP_001269644.1 Q68BL7-3
OLFML2AXM_006716989.3 linkuse as main transcriptc.758G>A p.Arg253Gln missense_variant 4/7 XP_006717052.1
OLFML2AXM_005251760.6 linkuse as main transcriptc.866G>A p.Arg289Gln missense_variant 5/7 XP_005251817.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OLFML2AENST00000373580.8 linkuse as main transcriptc.866G>A p.Arg289Gln missense_variant 5/81 NM_182487.4 ENSP00000362682.3 Q68BL7-1
OLFML2AENST00000288815.5 linkuse as main transcriptc.224G>A p.Arg75Gln missense_variant 2/51 ENSP00000288815.5 Q68BL7-3
OLFML2AENST00000331715.13 linkuse as main transcriptc.758G>A p.Arg253Gln missense_variant 4/52 ENSP00000336425.7 Q5JTM7

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000402
AC:
10
AN:
248710
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134846
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:
0.0000806
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000105
AC:
153
AN:
1461620
Hom.:
0
Cov.:
33
AF XY:
0.000103
AC XY:
75
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000122
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000823
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJul 13, 2021The c.866G>A (p.R289Q) alteration is located in exon 5 (coding exon 5) of the OLFML2A gene. This alteration results from a G to A substitution at nucleotide position 866, causing the arginine (R) at amino acid position 289 to be replaced by a glutamine (Q). 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
Benign
0.11
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.27
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.34
.;T;.
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.81
T;D;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Pathogenic
0.88
D
MutationAssessor
Uncertain
2.4
.;M;.
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.5
D;D;N
REVEL
Uncertain
0.53
Sift
Benign
0.030
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.97
D;P;D
Vest4
0.52, 0.54
MVP
0.80
MPC
0.60
ClinPred
0.79
D
GERP RS
6.1
Varity_R
0.48
gMVP
0.74

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: rs200657468; hg19: chr9-127563889; API