rs201895277
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017802.4(DNAAF5):c.2551G>A(p.Val851Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,612,796 control chromosomes in the GnomAD database, including 1 homozygotes. 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_017802.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.2551G>A | p.Val851Met | missense_variant | 13/13 | ENST00000297440.11 | |
DNAAF5 | XM_024446813.2 | c.2359G>A | p.Val787Met | missense_variant | 12/12 | ||
DNAAF5 | NR_075098.2 | n.2511G>A | non_coding_transcript_exon_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.2551G>A | p.Val851Met | missense_variant | 13/13 | 1 | NM_017802.4 | P1 | |
DNAAF5 | ENST00000403952.3 | c.826G>A | p.Val276Met | missense_variant | 6/6 | 1 | |||
DNAAF5 | ENST00000440747.5 | c.1957G>A | p.Val653Met | missense_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152200Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.0000440 AC: 11AN: 250156Hom.: 1 AF XY: 0.0000517 AC XY: 7AN XY: 135448
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460596Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 726588
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152200Hom.: 1 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74348
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2024 | The p.V851M variant (also known as c.2551G>A), located in coding exon 13 of the DNAAF5 gene, results from a G to A substitution at nucleotide position 2551. The valine at codon 851 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces valine with methionine at codon 851 of the DNAAF5 protein (p.Val851Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs201895277, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with DNAAF5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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