14-56804409-G-T
Variant names:
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
NM_021728.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.284
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]
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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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.312 AC: 47330AN: 151730Hom.: 7783 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
47330
AN:
151730
Hom.:
Cov.:
31
Gnomad AFR
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GnomAD2 exomes AF: 0.347 AC: 74531AN: 214732 AF XY: 0.348 show subpopulations
GnomAD2 exomes
AF:
AC:
74531
AN:
214732
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.341 AC: 481018AN: 1411498Hom.: 82760 Cov.: 28 AF XY: 0.341 AC XY: 238246AN XY: 698570 show subpopulations
GnomAD4 exome
AF:
AC:
481018
AN:
1411498
Hom.:
Cov.:
28
AF XY:
AC XY:
238246
AN XY:
698570
Gnomad4 AFR exome
AF:
AC:
6731
AN:
32444
Gnomad4 AMR exome
AF:
AC:
18432
AN:
42326
Gnomad4 ASJ exome
AF:
AC:
9344
AN:
23984
Gnomad4 EAS exome
AF:
AC:
7541
AN:
39208
Gnomad4 SAS exome
AF:
AC:
27349
AN:
80708
Gnomad4 FIN exome
AF:
AC:
16457
AN:
49556
Gnomad4 NFE exome
AF:
AC:
373850
AN:
1080514
Gnomad4 Remaining exome
AF:
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
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50-55
55-60
60-65
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70-75
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>80
Age
GnomAD4 genome AF: 0.312 AC: 47346AN: 151850Hom.: 7790 Cov.: 31 AF XY: 0.314 AC XY: 23326AN XY: 74238 show subpopulations
GnomAD4 genome
AF:
AC:
47346
AN:
151850
Hom.:
Cov.:
31
AF XY:
AC XY:
23326
AN XY:
74238
Gnomad4 AFR
AF:
AC:
0.213551
AN:
0.213551
Gnomad4 AMR
AF:
AC:
0.408381
AN:
0.408381
Gnomad4 ASJ
AF:
AC:
0.391354
AN:
0.391354
Gnomad4 EAS
AF:
AC:
0.210322
AN:
0.210322
Gnomad4 SAS
AF:
AC:
0.335963
AN:
0.335963
Gnomad4 FIN
AF:
AC:
0.342884
AN:
0.342884
Gnomad4 NFE
AF:
AC:
0.347054
AN:
0.347054
Gnomad4 OTH
AF:
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
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at