rs181484327
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_018076.5(ODAD2):c.26C>T(p.Thr9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. T9T) has been classified as Likely benign.
Frequency
Consequence
NM_018076.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD2 | NM_018076.5 | c.26C>T | p.Thr9Met | missense_variant | 2/20 | ENST00000305242.10 | |
LOC112268060 | XR_002957065.1 | n.220G>A | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.26C>T | p.Thr9Met | missense_variant | 2/20 | 1 | NM_018076.5 | P1 | |
ODAD2 | ENST00000673439.1 | c.26C>T | p.Thr9Met | missense_variant | 2/20 | P1 | |||
ODAD2 | ENST00000486279.2 | c.26C>T | p.Thr9Met | missense_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000159 AC: 40AN: 251408Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135882
GnomAD4 exome AF: 0.0000670 AC: 98AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727236
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74412
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 474582). This variant has not been reported in the literature in individuals affected with ARMC4-related conditions. This variant is present in population databases (rs181484327, gnomAD 0.1%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 9 of the ARMC4 protein (p.Thr9Met). - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at