chr2-26479491-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_194248.3(OTOF):c.2075G>A(p.Arg692Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000331 in 1,601,516 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R692R) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.2075G>A | p.Arg692Gln | missense_variant | 17/47 | ENST00000272371.7 | |
OTOF | NM_001287489.2 | c.2075G>A | p.Arg692Gln | missense_variant | 17/46 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2075G>A | p.Arg692Gln | missense_variant | 17/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000403946.7 | c.2075G>A | p.Arg692Gln | missense_variant | 17/46 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000493 AC: 11AN: 223068Hom.: 0 AF XY: 0.0000331 AC XY: 4AN XY: 120930
GnomAD4 exome AF: 0.0000324 AC: 47AN: 1449318Hom.: 0 Cov.: 34 AF XY: 0.0000292 AC XY: 21AN XY: 719962
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 29, 2013 | The Arg692Gln variant in OTOF has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg 692Gln variant is unlikely to impact the protein, though this information is not predictive enough to rule out pathogenicity. This variant has been identified i n 0.04% (2/4364) of African American chromosomes in a broad population by the NH LBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; dbSNP rs1479783 93). Although this variant has been seen in the general population, its frequenc y is not high enough to rule out a pathogenic role. Additional data is needed to determine the clinical significance of this variant. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.2075G>A (p.R692Q) alteration is located in exon 17 (coding exon 17) of the OTOF gene. This alteration results from a G to A substitution at nucleotide position 2075, causing the arginine (R) at amino acid position 692 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at