rs200291432
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_018139.3(DNAAF2):c.824C>T(p.Ala275Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,611,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_018139.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.824C>T | p.Ala275Val | missense_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.824C>T | p.Ala275Val | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.824C>T | p.Ala275Val | missense_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.824C>T | p.Ala275Val | missense_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000261 AC: 63AN: 241196Hom.: 0 AF XY: 0.000271 AC XY: 36AN XY: 132618
GnomAD4 exome AF: 0.000136 AC: 199AN: 1459318Hom.: 1 Cov.: 88 AF XY: 0.000134 AC XY: 97AN XY: 725964
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74488
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2015 | The p.A275V variant (also known as c.824C>T), located in coding exon 1 of the DNAAF2 gene, results from a C to T substitution at nucleotide position 824. The alanine at codon 275 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs200291432. This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6222 samples (12444 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. 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 variant remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Primary ciliary dyskinesia 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
DNAAF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 14, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at