8-98949091-C-G

Position:

• chr8-98949091-C-G

Variant summary

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

The NM_001142462.3(OSR2):​c.139C>G​(p.Gln47Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSR2 NM_001142462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.73

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/exons	MANE	UniProt
OSR2	NM_001142462.3	c.139C>G	p.Gln47Glu	missense_variant	2/4	ENST00000297565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSR2	ENST00000297565.9	c.139C>G	p.Gln47Glu	missense_variant	2/4	1	NM_001142462.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.139C>G (p.Q47E) alteration is located in exon 2 (coding exon 1) of the OSR2 gene. This alteration results from a C to G substitution at nucleotide position 139, causing the glutamine (Q) at amino acid position 47 to be replaced by a glutamic acid (E). 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	0.20
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	.;T;T;.;T;T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;.;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	.;.;L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.44	N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;T;D;D;D;D;D
Sift4G	Uncertain	0.021	D;T;T;T;T;T;T
Polyphen		0.35, 0.16, 0.48	.;B;B;P;B;.;.
Vest4		0.59
MutPred		0.68		.;Loss of catalytic residue at A45 (P = 0.3307);Loss of catalytic residue at A45 (P = 0.3307);Loss of catalytic residue at A45 (P = 0.3307);Loss of catalytic residue at A45 (P = 0.3307);.;Loss of catalytic residue at A45 (P = 0.3307);
MVP		0.50
MPC		1.3
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.45
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-99961319; COSMIC: COSV52557004; COSMIC: COSV52557004;