Variant 1-161984980-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015441.3(OLFML2B):c.1475G>A(p.Gly492Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000675 in 148,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 26)

Consequence

OLFML2B
NM_015441.3 missense, splice_region

Scores

Splicing: ADA: 0.9965

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

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]

OLFML2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML2B	NM_015441.3 linkuse as main transcript	c.1475G>A	p.Gly492Glu	missense_variant, splice_region_variant	7/8	ENST00000294794.8	NP_056256.1	Q68BL8-1
OLFML2B	NM_001347700.2 linkuse as main transcript	c.1481G>A	p.Gly494Glu	missense_variant, splice_region_variant	7/8		NP_001334629.1
OLFML2B	NM_001297713.2 linkuse as main transcript	c.1478G>A	p.Gly493Glu	missense_variant, splice_region_variant	7/8		NP_001284642.1	Q68BL8F2Z3N3B4DWE8
OLFML2B	XM_011509398.3 linkuse as main transcript	c.755G>A	p.Gly252Glu	missense_variant, splice_region_variant	4/5		XP_011507700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OLFML2B	ENST00000294794.8 linkuse as main transcript	c.1475G>A	p.Gly492Glu	missense_variant, splice_region_variant	7/8	1	NM_015441.3	ENSP00000294794.3	Q68BL8-1
OLFML2B	ENST00000367940.2 linkuse as main transcript	c.1478G>A	p.Gly493Glu	missense_variant, splice_region_variant	7/8	2		ENSP00000356917.2	F2Z3N3
OLFML2B	ENST00000367938.1 linkuse as main transcript	c.-77G>A		5_prime_UTR_variant	1/2	2		ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes

AF:

0.00000675

AC:

AN:

148160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000675

AC:

AN:

148160

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71942

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000149

Gnomad4 OTH

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 submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1475G>A (p.G492E) alteration is located in exon 7 (coding exon 7) of the OLFML2B gene. This alteration results from a G to A substitution at nucleotide position 1475, causing the glycine (G) at amino acid position 492 to be replaced by a glutamic acid (E). 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

0.74

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.057

T;D

Polyphen

0.98

D;D

Vest4

0.84

MutPred

0.45

.;Gain of helix (P = 0.0082);

MVP

0.89

MPC

0.63

ClinPred

0.95

GERP RS

4.3

Varity_R

0.43

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -4

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over