1-161984843-T-C

Variant summary

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

The NM_015441.3(OLFML2B):ā€‹c.1612A>Gā€‹(p.Thr538Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 28)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OLFML2BNM_015441.3 linkuse as main transcriptc.1612A>G p.Thr538Ala missense_variant 7/8 ENST00000294794.8
OLFML2BNM_001347700.2 linkuse as main transcriptc.1618A>G p.Thr540Ala missense_variant 7/8
OLFML2BNM_001297713.2 linkuse as main transcriptc.1615A>G p.Thr539Ala missense_variant 7/8
OLFML2BXM_011509398.3 linkuse as main transcriptc.892A>G p.Thr298Ala missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OLFML2BENST00000294794.8 linkuse as main transcriptc.1612A>G p.Thr538Ala missense_variant 7/81 NM_015441.3 P3Q68BL8-1
OLFML2BENST00000367940.2 linkuse as main transcriptc.1615A>G p.Thr539Ala missense_variant 7/82 A2
OLFML2BENST00000367938.1 linkuse as main transcriptc.61A>G p.Thr21Ala missense_variant 1/22 Q68BL8-2

Frequencies

GnomAD3 genomes
AF:
0.0000594
AC:
9
AN:
151638
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.000218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000119
AC:
3
AN:
251422
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00000958
AC:
14
AN:
1461846
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000594
AC:
9
AN:
151638
Hom.:
0
Cov.:
28
AF XY:
0.0000405
AC XY:
3
AN XY:
74010
show subpopulations
Gnomad4 AFR
AF:
0.000218
Gnomad4 AMR
AF:
0.00
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
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.00000824
AC:
1

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 GeneticsApr 01, 2024The c.1612A>G (p.T538A) alteration is located in exon 7 (coding exon 7) of the OLFML2B gene. This alteration results from a A to G substitution at nucleotide position 1612, causing the threonine (T) at amino acid position 538 to be replaced by an alanine (A). 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
0.26
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
T;D;.
Eigen
Benign
0.069
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Uncertain
0.089
D
MetaRNN
Uncertain
0.49
T;T;T
MetaSVM
Uncertain
0.081
D
MutationAssessor
Benign
1.4
L;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Uncertain
0.39
Sift
Uncertain
0.0070
D;D;T
Sift4G
Benign
0.11
T;T;T
Polyphen
0.12
B;P;.
Vest4
0.71
MVP
0.87
MPC
0.33
ClinPred
0.37
T
GERP RS
4.2
Varity_R
0.20
gMVP
0.63

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: rs776291655; hg19: chr1-161954633; API