Variant chr14-56801725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_021728.4(OTX2):c.*10G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 1,613,006 control chromosomes in the GnomAD database, including 6,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 380 hom., cov: 32)

Exomes 𝑓: 0.085 ( 6024 hom. )

Consequence

OTX2
NM_021728.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.02

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 14-56801725-C-T is Benign according to our data. Variant chr14-56801725-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 288866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0947 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.*10G>A		3_prime_UTR_variant	5/5	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.*10G>A		3_prime_UTR_variant	5/5		NM_021728.4	ENSP00000500115	A1	P32243-2

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9564

AN:

152122

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.0698

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0532

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0966

Gnomad OTH

AF:

0.0742

GnomAD3 exomes

AF:

0.0648

AC:

16225

AN:

250220

Hom.:

692

AF XY:

0.0663

AC XY:

8998

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.0502

Gnomad ASJ exome

AF:

0.0717

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0515

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0785

GnomAD4 exome

AF:

0.0852

AC:

124422

AN:

1460766

Hom.:

6024

Cov.:

AF XY:

0.0837

AC XY:

60801

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.0513

Gnomad4 ASJ exome

AF:

0.0698

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0511

Gnomad4 NFE exome

AF:

0.0993

Gnomad4 OTH exome

AF:

0.0749

GnomAD4 genome

AF:

0.0628

AC:

9557

AN:

152240

Hom.:

380

Cov.:

AF XY:

0.0607

AC XY:

4518

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.0696

Gnomad4 ASJ

AF:

0.0706

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.0532

Gnomad4 NFE

AF:

0.0966

Gnomad4 OTH

AF:

0.0725

Alfa

AF:

0.0913

Hom.:

801

Bravo

AF:

0.0639

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

OTX2-Related Syndromic Microphthalmia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Syndromic microphthalmia type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 20, 2016

- -

Pituitary hormone deficiency, combined, 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Retinal dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.86

Splicing

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