8-98951668-C-T

Variant names:

• chr8-98951668-C-T
• rs895173449
• ENST00000435298.6:c.824C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_053001.4(OSR2):​c.824C>T​(p.Thr275Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: OSR2 NM_053001.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.98

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34566742).
• BP6: Variant 8-98951668-C-T is Benign according to our data. Variant chr8-98951668-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3412631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSR2	NM_001142462.3	c.906C>T	p.His302His	synonymous_variant	Exon 4 of 4	ENST00000297565.9	NP_001135934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSR2	ENST00000435298.6	c.824C>T	p.Thr275Ile	missense_variant	Exon 4 of 4	1		ENSP00000402862.2
OSR2	ENST00000297565.9	c.906C>T	p.His302His	synonymous_variant	Exon 4 of 4	1	NM_001142462.3	ENSP00000297565.4
OSR2	ENST00000457907.3	c.1269C>T	p.His423His	synonymous_variant	Exon 5 of 5	2		ENSP00000414657.2
OSR2	ENST00000522510.5	c.906C>T	p.His302His	synonymous_variant	Exon 5 of 5	2		ENSP00000430780.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461460 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74352

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 27, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.2	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.23		Loss of disorder (P = 0.0351);
MVP		0.57
ClinPred		0.93	D
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

LitVar

Other links and lift over

dbSNP: rs895173449; hg19: chr8-99963896;