rs376424270
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018076.5(ODAD2):c.1318C>T(p.Arg440Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,605,036 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. R440H) has been classified as Uncertain significance.
Frequency
Consequence
NM_018076.5 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 |
---|---|---|---|---|---|---|---|
ODAD2 | NM_018076.5 | c.1318C>T | p.Arg440Cys | missense_variant | 10/20 | ENST00000305242.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.1318C>T | p.Arg440Cys | missense_variant | 10/20 | 1 | NM_018076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000837 AC: 21AN: 250748Hom.: 0 AF XY: 0.0000959 AC XY: 13AN XY: 135490
GnomAD4 exome AF: 0.000184 AC: 267AN: 1452908Hom.: 0 Cov.: 27 AF XY: 0.000178 AC XY: 129AN XY: 723220
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2022 | The c.1318C>T (p.R440C) alteration is located in exon 10 (coding exon 9) of the ARMC4 gene. This alteration results from a C to T substitution at nucleotide position 1318, causing the arginine (R) at amino acid position 440 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 440 of the ARMC4 protein (p.Arg440Cys). This variant is present in population databases (rs376424270, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ARMC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 541496). 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 disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at