Genetic Variant OSR2:p.Thr275Ile (chr8-98951668-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_053001.4(OSR2):c.824C>T(p.Thr275Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

OSR2
NM_053001.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.98

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34566742).

BP6

Variant 8-98951668-C-T is Benign according to our data. Variant chr8-98951668-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3412631.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053001.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSR2	NM_001142462.3	MANE Select	c.906C>T	p.His302His	synonymous	Exon 4 of 4	NP_001135934.1	Q8N2R0-1
OSR2	NM_053001.4		c.824C>T	p.Thr275Ile	missense	Exon 4 of 4	NP_443727.2	Q8N2R0-2
OSR2	NM_001394683.1		c.680C>T	p.Thr227Ile	missense	Exon 4 of 4	NP_001381612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSR2	ENST00000435298.6	TSL:1	c.824C>T	p.Thr275Ile	missense	Exon 4 of 4	ENSP00000402862.2	Q8N2R0-2
OSR2	ENST00000297565.9	TSL:1 MANE Select	c.906C>T	p.His302His	synonymous	Exon 4 of 4	ENSP00000297565.4	Q8N2R0-1
OSR2	ENST00000457907.3	TSL:2	c.1269C>T	p.His423His	synonymous	Exon 5 of 5	ENSP00000414657.2	Q8N2R0-3

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000478

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111794

Other (OTH)

AF:

0.0000828

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68050

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000102

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.48

M_CAP

Benign

0.019

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.2

PhyloP100

6.0

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.33

MutPred

0.23

Loss of disorder (P = 0.0351)

MVP

0.57

ClinPred

0.93

GERP RS

5.3

Mutation Taster

=11/89

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over