rs547924178
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_018139.3(DNAAF2):c.1597A>G(p.Thr533Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,980 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 Uncertain significance (★).
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.1597A>G | p.Thr533Ala | missense_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.1597A>G | p.Thr533Ala | missense_variant | 1/2 | ||
DNAAF2 | NM_001378453.1 | c.-275A>G | 5_prime_UTR_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.1597A>G | p.Thr533Ala | missense_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.1597A>G | p.Thr533Ala | missense_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000112 AC: 28AN: 251000Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135692
GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461688Hom.: 0 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727126
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74462
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2017 | This variant has not been reported in the literature in individuals with a DNAAF2-related disease. In summary, this variant has uncertain impact on DNAAF2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is present in population databases (rs547924178, ExAC 0.1%). This sequence change replaces threonine with alanine at codon 533 of the DNAAF2 protein (p.Thr533Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at