Variant 1-161984016-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015441.3(OLFML2B):c.1912G>A(p.Asp638Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2052103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML2B	NM_015441.3 linkuse as main transcript	c.1912G>A	p.Asp638Asn	missense_variant	8/8	ENST00000294794.8	NP_056256.1	Q68BL8-1
OLFML2B	NM_001347700.2 linkuse as main transcript	c.1918G>A	p.Asp640Asn	missense_variant	8/8		NP_001334629.1
OLFML2B	NM_001297713.2 linkuse as main transcript	c.1915G>A	p.Asp639Asn	missense_variant	8/8		NP_001284642.1	Q68BL8F2Z3N3B4DWE8
OLFML2B	XM_011509398.3 linkuse as main transcript	c.1192G>A	p.Asp398Asn	missense_variant	5/5		XP_011507700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OLFML2B	ENST00000294794.8 linkuse as main transcript	c.1912G>A	p.Asp638Asn	missense_variant	8/8	1	NM_015441.3	ENSP00000294794.3	Q68BL8-1
OLFML2B	ENST00000367940.2 linkuse as main transcript	c.1915G>A	p.Asp639Asn	missense_variant	8/8	2		ENSP00000356917.2	F2Z3N3
OLFML2B	ENST00000367938.1 linkuse as main transcript	c.361G>A	p.Asp121Asn	missense_variant	2/2	2		ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251418

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727240

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:

0.0000414

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 04, 2024

The c.1912G>A (p.D638N) alteration is located in exon 8 (coding exon 8) of the OLFML2B gene. This alteration results from a G to A substitution at nucleotide position 1912, causing the aspartic acid (D) at amino acid position 638 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

Benign

0.086

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;T;.

Eigen

Benign

0.081

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.064

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Uncertain

-0.058

MutationAssessor

Benign

0.28

N;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.43

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.28

B;D;.

Vest4

0.23

MutPred

0.36

.;Loss of loop (P = 0.0986);.;

MVP

0.82

MPC

0.24

ClinPred

0.76

GERP RS

5.4

Varity_R

0.13

gMVP

0.35

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