8-98949209-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSR2	NM_001142462.3	c.257C>G	p.Pro86Arg	missense_variant	Exon 2 of 4	ENST00000297565.9	NP_001135934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000297565.9	c.257C>G	p.Pro86Arg	missense_variant	Exon 2 of 4	1	NM_001142462.3	ENSP00000297565.4

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

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: 0.0000192

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;.;D;T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;.;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;L;L;L;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N;D;D;D;D;D;D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D
Polyphen		0.97, 0.94, 0.99	.;D;P;D;P;.;.
Vest4		0.75
MutPred		0.46		.;Gain of catalytic residue at P86 (P = 0.1015);Gain of catalytic residue at P86 (P = 0.1015);Gain of catalytic residue at P86 (P = 0.1015);Gain of catalytic residue at P86 (P = 0.1015);.;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

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

Other links and lift over

dbSNP: rs201438766; hg19: chr8-99961437;