14-56801394-TG-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_021728.4(OTX2):c.*340delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 370,246 control chromosomes in the GnomAD database, including 292 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 95 hom., cov: 32)

Exomes 𝑓: 0.030 ( 197 hom. )

Consequence

OTX2
NM_021728.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.96

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

syndromic microphthalmia type 5
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Orphanet
pituitary hormone deficiency, combined, 6
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
combined pituitary hormone deficiencies, genetic form
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated anophthalmia-microphthalmia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
patterned macular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
septooptic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

OTX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 14-56801394-TG-T is Benign according to our data. Variant chr14-56801394-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 313414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTX2	NM_021728.4 link	c.*340delC		3_prime_UTR_variant	Exon 5 of 5	ENST00000672264.2	NP_068374.1	P32243-2F1T0D1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTX2	ENST00000672264.2 link	c.*340delC		3_prime_UTR_variant	Exon 5 of 5		NM_021728.4	ENSP00000500115.1		P32243-2

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4104

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0360

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0570

Gnomad FIN

AF:

0.0397

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0287

GnomAD4 exome

AF:

0.0296

AC:

6458

AN:

217964

Hom.:

197

Cov.:

AF XY:

0.0316

AC XY:

3727

AN XY:

117798

show subpopulations

African (AFR)

AF:

0.0192

AC:

126

AN:

6568

American (AMR)

AF:

0.0309

AC:

316

AN:

10222

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

AN:

5808

East Asian (EAS)

AF:

0.124

AC:

1266

AN:

10216

South Asian (SAS)

AF:

0.0473

AC:

1702

AN:

36014

European-Finnish (FIN)

AF:

0.0391

AC:

394

AN:

10086

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

834

European-Non Finnish (NFE)

AF:

0.0178

AC:

2264

AN:

126844

Other (OTH)

AF:

0.0275

AC:

313

AN:

11372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

299

598

896

1195

1494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0270

AC:

4114

AN:

152282

Hom.:

Cov.:

AF XY:

0.0295

AC XY:

2200

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0195

AC:

811

AN:

41566

American (AMR)

AF:

0.0358

AC:

548

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3470

East Asian (EAS)

AF:

0.128

AC:

660

AN:

5162

South Asian (SAS)

AF:

0.0568

AC:

274

AN:

4824

European-Finnish (FIN)

AF:

0.0397

AC:

422

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1270

AN:

68022

Other (OTH)

AF:

0.0284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

194

388

581

775

969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.101

AC:

349

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

OTX2-Related Syndromic Microphthalmia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Syndromic Microphthalmia, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 14, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Retinal dystrophy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Combined Pituitary Hormone Deficiency, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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14-56801394-TG-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over