rs550895099
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_001292063.2(OTOG):c.2562-14G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,550,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
OTOG
NM_001292063.2 splice_polypyrimidine_tract, intron
NM_001292063.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.182
Genes affected
OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 11-17576854-G-A is Benign according to our data. Variant chr11-17576854-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.2562-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000399397.6 | |||
OTOG | NM_001277269.2 | c.2598-14G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.2562-14G>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001292063.2 | P2 | |||
OTOG | ENST00000399391.7 | c.2598-14G>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152134Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000121 AC: 18AN: 148672Hom.: 0 AF XY: 0.000137 AC XY: 11AN XY: 80034
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GnomAD4 exome AF: 0.000104 AC: 145AN: 1398002Hom.: 0 Cov.: 31 AF XY: 0.000104 AC XY: 72AN XY: 689516
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74438
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2015 | c.2598-14G>A in intron 21 of OTOG: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at