chr2-26477025-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_194248.3(OTOF):c.2542G>A(p.Asp848Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,433,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2542G>A | p.Asp848Asn | missense_variant | Exon 22 of 47 | 1 | NM_194248.3 | ENSP00000272371.2 | ||
OTOF | ENST00000339598.8 | c.301G>A | p.Asp101Asn | missense_variant | Exon 5 of 29 | 1 | NM_194323.3 | ENSP00000344521.3 |
Frequencies
GnomAD3 genomes AF: 0.000129 AC: 19AN: 147396Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000448 AC: 10AN: 223226Hom.: 0 AF XY: 0.0000330 AC XY: 4AN XY: 121034
GnomAD4 exome AF: 0.0000140 AC: 18AN: 1285788Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 8AN XY: 643578
GnomAD4 genome AF: 0.000115 AC: 17AN: 147528Hom.: 0 Cov.: 31 AF XY: 0.0000973 AC XY: 7AN XY: 71934
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Asp848Asn has been previously reported in 2 individuals with hearing loss, 1 of whom also had a second missense variant in OTOF (Sloan-Heggen 2016, LMM un published data). This variant has also been identified in 0.1% (8/6858) of Afric an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs147865867); however, this frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest the variant may impact the protein, though this information is not pred ictive enough to determine pathogenicity. In summary, the clinical significance of the p.Asp848Asn variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at