rs143513621
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_018076.5(ODAD2):c.1277G>A(p.Ser426Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000668 in 1,600,804 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. S426S) 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.1277G>A | p.Ser426Asn | missense_variant | 10/20 | ENST00000305242.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.1277G>A | p.Ser426Asn | missense_variant | 10/20 | 1 | NM_018076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000121 AC: 30AN: 248160Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 134098
GnomAD4 exome AF: 0.0000366 AC: 53AN: 1448524Hom.: 0 Cov.: 26 AF XY: 0.0000291 AC XY: 21AN XY: 721108
GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74462
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 426 of the ARMC4 protein (p.Ser426Asn). This variant is present in population databases (rs143513621, gnomAD 0.1%). 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: 474572). 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. 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. - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2021 | 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