Variant 1-161984867-C-A 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.1588G>T(p.Val530Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,848 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: not found (cov: 27)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

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:

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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, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFML2B	NM_015441.3 linkuse as main transcript	c.1588G>T	p.Val530Leu	missense_variant	7/8	ENST00000294794.8
OLFML2B	NM_001347700.2 linkuse as main transcript	c.1594G>T	p.Val532Leu	missense_variant	7/8
OLFML2B	NM_001297713.2 linkuse as main transcript	c.1591G>T	p.Val531Leu	missense_variant	7/8
OLFML2B	XM_011509398.3 linkuse as main transcript	c.868G>T	p.Val290Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML2B	ENST00000294794.8 linkuse as main transcript	c.1588G>T	p.Val530Leu	missense_variant	7/8	1	NM_015441.3	P3	Q68BL8-1
OLFML2B	ENST00000367940.2 linkuse as main transcript	c.1591G>T	p.Val531Leu	missense_variant	7/8	2		A2
OLFML2B	ENST00000367938.1 linkuse as main transcript	c.37G>T	p.Val13Leu	missense_variant	1/2	2			Q68BL8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 24, 2022

The c.1588G>T (p.V530L) alteration is located in exon 7 (coding exon 7) of the OLFML2B gene. This alteration results from a G to T substitution at nucleotide position 1588, causing the valine (V) at amino acid position 530 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

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;D;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.3

N;N;N

REVEL

Pathogenic

0.80

Sift

Benign

0.059

T;T;T

Sift4G

Uncertain

0.0090

D;D;T

Polyphen

0.75

P;P;.

Vest4

0.82

MutPred

0.61

.;Gain of catalytic residue at V531 (P = 0.0722);.;

MVP

0.89

MPC

0.45

ClinPred

0.93

GERP RS

4.3

Varity_R

0.26

gMVP

0.72

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.

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