Genetic Variant OSR2:p.Pro86Leu (chr8-98949209-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001142462.3(OSR2):c.257C>T(p.Pro86Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000044 in 1,591,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

OSR2
NM_001142462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

OSR2 (HGNC:15830): (odd-skipped related transciption factor 2) OSR2 is a mammalian homolog of the Drosophila odd-skipped family of transcription factors (Lan et al., 2004 [PubMed 15175245]).[supplied by OMIM, Mar 2008]

OSR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32570565).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSR2	NM_001142462.3 link	c.257C>T	p.Pro86Leu	missense_variant	Exon 2 of 4	ENST00000297565.9	NP_001135934.1	Q8N2R0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000297565.9 link	c.257C>T	p.Pro86Leu	missense_variant	Exon 2 of 4	1	NM_001142462.3	ENSP00000297565.4		Q8N2R0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000173

AC:

AN:

230820

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124142

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000301

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:

0.00000957

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

1439356

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

713114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.0000230

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:

9.10e-7

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

Bravo

AF:

0.0000151

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.257C>T (p.P86L) alteration is located in exon 2 (coding exon 1) of the OSR2 gene. This alteration results from a C to T substitution at nucleotide position 257, causing the proline (P) at amino acid position 86 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

.;T;T;.;T;T;T

Eigen

Benign

0.056

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;.;D;D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.33

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;L;L;L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.1

N;D;N;D;N;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.014

D;D;D;D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D

Polyphen

0.032, 0.91, 0.98

.;B;P;D;P;.;.

Vest4

0.66

MutPred

0.42

.;Loss of glycosylation at T91 (P = 0.1353);Loss of glycosylation at T91 (P = 0.1353);Loss of glycosylation at T91 (P = 0.1353);Loss of glycosylation at T91 (P = 0.1353);.;Loss of glycosylation at T91 (P = 0.1353);

MVP

0.42

MPC

0.77

ClinPred

0.77

GERP RS

3.7

Varity_R

0.095

gMVP

0.76

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