8-98949209-C-G

Variant names:

• chr8-98949209-C-G
• rs201438766
• NM_001142462.3:c.257C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142462.3(OSR2):​c.257C>G​(p.Pro86Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,439,358 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P86L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OSR2 NM_001142462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142462.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSR2	NM_001142462.3	MANE Select	c.257C>G	p.Pro86Arg	missense	Exon 2 of 4	NP_001135934.1	Q8N2R0-1
	OSR2	NM_001286841.2		c.620C>G	p.Pro207Arg	missense	Exon 3 of 5	NP_001273770.1	Q8N2R0-3
	OSR2	NM_053001.4		c.257C>G	p.Pro86Arg	missense	Exon 2 of 4	NP_443727.2	Q8N2R0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSR2	ENST00000297565.9	TSL:1 MANE Select	c.257C>G	p.Pro86Arg	missense	Exon 2 of 4	ENSP00000297565.4	Q8N2R0-1
	OSR2	ENST00000523368.5	TSL:1	c.257C>G	p.Pro86Arg	missense	Exon 2 of 3	ENSP00000430041.1	E5RH04
	OSR2	ENST00000435298.6	TSL:1	c.257C>G	p.Pro86Arg	missense	Exon 2 of 4	ENSP00000402862.2	Q8N2R0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439358 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 713116

African (AFR) AF: 0.00 AC: 0 AN: 33196

American (AMR) AF: 0.00 AC: 0 AN: 43436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24440

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 82466

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099176

Other (OTH) AF: 0.00 AC: 0 AN: 59374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.75
MutPred		0.46		Gain of catalytic residue at P86 (P = 0.1015)
MVP		0.45
MPC		0.81
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.40
gMVP		0.80
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs201438766; hg19: chr8-99961437;