chr1-161983694-T-A

Variant summary

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

The NM_015441.3(OLFML2B):​c.2234A>T​(p.His745Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OLFML2B
NM_015441.3 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96
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.2234A>T p.His745Leu missense_variant 8/8 ENST00000294794.8
OLFML2BNM_001347700.2 linkuse as main transcriptc.2240A>T p.His747Leu missense_variant 8/8
OLFML2BNM_001297713.2 linkuse as main transcriptc.2237A>T p.His746Leu missense_variant 8/8
OLFML2BXM_011509398.3 linkuse as main transcriptc.1514A>T p.His505Leu missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OLFML2BENST00000294794.8 linkuse as main transcriptc.2234A>T p.His745Leu missense_variant 8/81 NM_015441.3 P3Q68BL8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsOct 30, 2023The c.2234A>T (p.H745L) alteration is located in exon 8 (coding exon 8) of the OLFML2B gene. This alteration results from a A to T substitution at nucleotide position 2234, causing the histidine (H) at amino acid position 745 to be replaced by a leucine (L). 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
0.25
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Uncertain
0.52
D;D;.
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Benign
0.55
N;.;.
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-4.2
D;D;D
REVEL
Uncertain
0.60
Sift
Benign
0.084
T;T;D
Sift4G
Benign
0.20
T;T;D
Polyphen
0.80
P;P;.
Vest4
0.49
MutPred
0.54
.;Loss of disorder (P = 0.0036);.;
MVP
0.88
MPC
0.52
ClinPred
0.85
D
GERP RS
4.2
Varity_R
0.22
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-161953484; API