8-98951616-G-A

Position:

• chr8-98951616-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142462.3(OSR2):​c.854G>A​(p.Ser285Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSR2 NM_001142462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06555614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSR2	NM_001142462.3	c.854G>A	p.Ser285Asn	missense_variant	4/4	ENST00000297565.9	NP_001135934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000297565.9	c.854G>A	p.Ser285Asn	missense_variant	4/4	1	NM_001142462.3	ENSP00000297565.4
OSR2	ENST00000435298.6	c.772G>A	p.Ala258Thr	missense_variant	4/4	1		ENSP00000402862.2
OSR2	ENST00000457907.3	c.1217G>A	p.Ser406Asn	missense_variant	5/5	2		ENSP00000414657.2
OSR2	ENST00000522510.5	c.854G>A	p.Ser285Asn	missense_variant	5/5	2		ENSP00000430780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Mar 30, 2024

The c.854G>A (p.S285N) alteration is located in exon 4 (coding exon 3) of the OSR2 gene. This alteration results from a G to A substitution at nucleotide position 854, causing the serine (S) at amino acid position 285 to be replaced by an asparagine (N). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.98
Eigen	Benign	-0.073
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.066
Sift	Benign	0.57	T
Sift4G	Benign	0.095	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.14		Gain of glycosylation at A258 (P = 0.0067);
MVP		0.38
ClinPred		0.97	D
GERP RS		3.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-99963844;