chr1-161983763-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015441.3(OLFML2B):​c.2165C>A​(p.Thr722Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,922 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

8
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.86
Variant links:
Genes affected
OLFML2B (HGNC:24558): (olfactomedin like 2B) This gene encodes an olfactomedin domain-containing protein. Most olfactomedin domain-containing proteins are secreted glycoproteins. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OLFML2BNM_015441.3 linkuse as main transcriptc.2165C>A p.Thr722Asn missense_variant 8/8 ENST00000294794.8
OLFML2BNM_001347700.2 linkuse as main transcriptc.2171C>A p.Thr724Asn missense_variant 8/8
OLFML2BNM_001297713.2 linkuse as main transcriptc.2168C>A p.Thr723Asn missense_variant 8/8
OLFML2BXM_011509398.3 linkuse as main transcriptc.1445C>A p.Thr482Asn missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OLFML2BENST00000294794.8 linkuse as main transcriptc.2165C>A p.Thr722Asn missense_variant 8/81 NM_015441.3 P3Q68BL8-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152028
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251494
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000205
AC:
3
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152028
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsMar 18, 2024The c.2165C>A (p.T722N) alteration is located in exon 8 (coding exon 8) of the OLFML2B gene. This alteration results from a C to A substitution at nucleotide position 2165, causing the threonine (T) at amino acid position 722 to be replaced by an asparagine (N). 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
0.75
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;D;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Uncertain
2.4
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Pathogenic
0.68
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0020
D;D;T
Polyphen
1.0
D;D;.
Vest4
0.91
MutPred
0.50
.;Loss of phosphorylation at T723 (P = 0.0334);.;
MVP
0.93
MPC
0.60
ClinPred
0.97
D
GERP RS
5.6
Varity_R
0.67
gMVP
0.79

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: rs1482872581; hg19: chr1-161953553; API