8-98951659-G-A

Position:

• chr8-98951659-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000435298.6(OSR2):​c.815G>A​(p.Cys272Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSR2 ENST00000435298.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.60

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=0.15336087).
• BP6: Variant 8-98951659-G-A is Benign according to our data. Variant chr8-98951659-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3303624.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSR2	NM_001142462.3	c.897G>A	p.Leu299=	synonymous_variant	4/4	ENST00000297565.9	NP_001135934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000435298.6	c.815G>A	p.Cys272Tyr	missense_variant	4/4	1		ENSP00000402862
OSR2	ENST00000297565.9	c.897G>A	p.Leu299=	synonymous_variant	4/4	1	NM_001142462.3	ENSP00000297565	P1
OSR2	ENST00000457907.3	c.1260G>A	p.Leu420=	synonymous_variant	5/5	2		ENSP00000414657
OSR2	ENST00000522510.5	c.897G>A	p.Leu299=	synonymous_variant	5/5	2		ENSP00000430780	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.95
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	D;D;D;D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.23
Sift	Benign	0.14	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.20
MutPred		0.46		Gain of phosphorylation at C272 (P = 0.0417);
MVP		0.37
ClinPred		0.34	T
GERP RS		5.3

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: chr8-99963887;