NM_001142462.3:c.778A>C

Variant names:

• chr8-98951540-A-C
• rs1422909819
• NM_001142462.3:c.778A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142462.3(OSR2):​c.778A>C​(p.Thr260Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T260A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSR2 NM_001142462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16

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.778A>C	p.Thr260Pro	missense_variant	Exon 4 of 4	ENST00000297565.9	NP_001135934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000297565.9	c.778A>C	p.Thr260Pro	missense_variant	Exon 4 of 4	1	NM_001142462.3	ENSP00000297565.4
OSR2	ENST00000435298.6	c.757-61A>C		intron_variant	Intron 3 of 3	1		ENSP00000402862.2
OSR2	ENST00000457907.3	c.1141A>C	p.Thr381Pro	missense_variant	Exon 5 of 5	2		ENSP00000414657.2
OSR2	ENST00000522510.5	c.778A>C	p.Thr260Pro	missense_variant	Exon 5 of 5	2		ENSP00000430780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;.;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.27
Sift	Benign	0.17	T;T;T
Sift4G	Uncertain	0.039	D;T;T
Polyphen		0.99	.;D;D
Vest4		0.53
MutPred		0.47		.;Gain of catalytic residue at P259 (P = 0.0428);Gain of catalytic residue at P259 (P = 0.0428);
MVP		0.60
MPC		1.1
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.72
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1422909819; hg19: chr8-99963768;