chr19-48318548-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001364171.2(ODAD1):c.199C>T(p.Arg67Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000593 in 1,551,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001364171.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD1 | NM_001364171.2 | c.199C>T | p.Arg67Trp | missense_variant | 5/16 | ENST00000674294.1 | |
ODAD1 | NM_144577.4 | c.88C>T | p.Arg30Trp | missense_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD1 | ENST00000674294.1 | c.199C>T | p.Arg67Trp | missense_variant | 5/16 | NM_001364171.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152058Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000453 AC: 7AN: 154556Hom.: 0 AF XY: 0.0000244 AC XY: 2AN XY: 81962
GnomAD4 exome AF: 0.0000615 AC: 86AN: 1399258Hom.: 0 Cov.: 31 AF XY: 0.0000681 AC XY: 47AN XY: 690128
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152058Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74248
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2021 | This sequence change replaces arginine with tryptophan at codon 30 of the CCDC114 protein (p.Arg30Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs763939366, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with CCDC114-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2022 | The p.R30W variant (also known as c.88C>T), located in coding exon 2 of the CCDC114 gene, results from a C to T substitution at nucleotide position 88. The arginine at codon 30 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at