Variant 8-98949197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001142462.3(OSR2):c.245G>A(p.Arg82His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,592,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

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: 8.05

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 -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSR2	NM_001142462.3 link	c.245G>A	p.Arg82His	missense_variant	2/4	ENST00000297565.9	NP_001135934.1	Q8N2R0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000297565.9 link	c.245G>A	p.Arg82His	missense_variant	2/4	1	NM_001142462.3	ENSP00000297565.4		Q8N2R0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230188

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123936

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000956

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

1440040

Hom.:

Cov.:

AF XY:

0.00000841

AC XY:

AN XY:

713680

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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:

0.00000455

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.00000828

AC:

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

Jan 26, 2022

The c.245G>A (p.R82H) alteration is located in exon 2 (coding exon 1) of the OSR2 gene. This alteration results from a G to A substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.049

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

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.58

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

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

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.024

D;D;T;D;T;D;D

Sift4G

Uncertain

0.010

D;D;T;T;T;T;T

Polyphen

1.0

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

Vest4

0.76

MutPred

0.50

.;Loss of methylation at R82 (P = 0.0368);Loss of methylation at R82 (P = 0.0368);Loss of methylation at R82 (P = 0.0368);Loss of methylation at R82 (P = 0.0368);.;Loss of methylation at R82 (P = 0.0368);

MVP

0.53

MPC

1.0

ClinPred

0.91

GERP RS

3.6

Varity_R

0.12

gMVP

0.57

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