14-56804409-G-T

Variant summary

Our verdict is Benign. The variant received -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

2

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
OTX2NM_021728.4 linkc.98-46C>A intron_variant Intron 3 of 4 ENST00000672264.2 NP_068374.1 P32243-2F1T0D1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTX2ENST00000672264.2 linkc.98-46C>A intron_variant Intron 3 of 4 NM_021728.4 ENSP00000500115.1 P32243-2

Frequencies

GnomAD3 genomes
AF:
0.312
AC:
47330
AN:
151730
Hom.:
7783
Cov.:
31
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
GnomAD2 exomes
AF:
0.347
AC:
74531
AN:
214732
AF XY:
0.348
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 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.:
28
AF XY:
0.341
AC XY:
238246
AN XY:
698570
show subpopulations
Gnomad4 AFR exome
AF:
0.207
AC:
6731
AN:
32444
Gnomad4 AMR exome
AF:
0.435
AC:
18432
AN:
42326
Gnomad4 ASJ exome
AF:
0.390
AC:
9344
AN:
23984
Gnomad4 EAS exome
AF:
0.192
AC:
7541
AN:
39208
Gnomad4 SAS exome
AF:
0.339
AC:
27349
AN:
80708
Gnomad4 FIN exome
AF:
0.332
AC:
16457
AN:
49556
Gnomad4 NFE exome
AF:
0.346
AC:
373850
AN:
1080514
Gnomad4 Remaining exome
AF:
0.339
AC:
19739
AN:
58280
Heterozygous variant carriers
0
16222
32444
48665
64887
81109
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
12028
24056
36084
48112
60140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.312
AC:
47346
AN:
151850
Hom.:
7790
Cov.:
31
AF XY:
0.314
AC XY:
23326
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.214
AC:
0.213551
AN:
0.213551
Gnomad4 AMR
AF:
0.408
AC:
0.408381
AN:
0.408381
Gnomad4 ASJ
AF:
0.391
AC:
0.391354
AN:
0.391354
Gnomad4 EAS
AF:
0.210
AC:
0.210322
AN:
0.210322
Gnomad4 SAS
AF:
0.336
AC:
0.335963
AN:
0.335963
Gnomad4 FIN
AF:
0.343
AC:
0.342884
AN:
0.342884
Gnomad4 NFE
AF:
0.347
AC:
0.347054
AN:
0.347054
Gnomad4 OTH
AF:
0.325
AC:
0.325261
AN:
0.325261
Heterozygous variant carriers
0
1557
3114
4671
6228
7785
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
482
964
1446
1928
2410
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.330
Hom.:
1661
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
3.3
DANN
Benign
0.78
Mutation Taster
=100/0
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs2277499; hg19: chr14-57271127; COSMIC: COSV59767049; API