Variant rs2277499 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021728.4(OTX2):c.98-46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,563,348 control chromosomes in the GnomAD database, including 90,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7790 hom., cov: 31)

Exomes 𝑓: 0.34 ( 82760 hom. )

Consequence

OTX2
NM_021728.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.284

Variant links:

Genes affected

OTX2 (HGNC:8522): (orthodenticle homeobox 2) This gene encodes a member of the bicoid subfamily of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and plays a role in brain, craniofacial, and sensory organ development. The encoded protein also influences the proliferation and differentiation of dopaminergic neuronal progenitor cells during mitosis. Mutations in this gene cause syndromic microphthalmia 5 (MCOPS5) and combined pituitary hormone deficiency 6 (CPHD6). This gene is also suspected of having an oncogenic role in medulloblastoma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Pseudogenes of this gene are known to exist on chromosomes two and nine. [provided by RefSeq, Jul 2012]

OTX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-56804409-G-T is Benign according to our data. Variant chr14-56804409-G-T is described in ClinVar as [Benign]. Clinvar id is 1292627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-56804409-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTX2	NM_021728.4 linkuse as main transcript	c.98-46C>A		intron_variant		ENST00000672264.2	NP_068374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTX2	ENST00000672264.2 linkuse as main transcript	c.98-46C>A		intron_variant			NM_021728.4	ENSP00000500115	A1	P32243-2

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47330

AN:

151730

Hom.:

7783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.324

GnomAD3 exomes

AF:

0.347

AC:

74531

AN:

214732

Hom.:

12976

AF XY:

0.348

AC XY:

40676

AN XY:

116808

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.215

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.341

AC:

481018

AN:

1411498

Hom.:

82760

Cov.:

AF XY:

0.341

AC XY:

238246

AN XY:

698570

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.346

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.312

AC:

47346

AN:

151850

Hom.:

7790

Cov.:

AF XY:

0.314

AC XY:

23326

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.408

Gnomad4 ASJ

AF:

0.391

Gnomad4 EAS

AF:

0.210

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.333

Hom.:

1650

Bravo

AF:

0.315

Asia WGS

AF:

0.296

AC:

1029

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.3

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over