rs772102523
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000297440.11(DNAAF5):c.2375G>A(p.Arg792Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000297440.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.2375G>A | p.Arg792Gln | missense_variant | 12/13 | ENST00000297440.11 | NP_060272.3 | |
DNAAF5 | XM_024446813.2 | c.2239+4926G>A | intron_variant | XP_024302581.1 | ||||
DNAAF5 | NR_075098.2 | n.2335G>A | non_coding_transcript_exon_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.2375G>A | p.Arg792Gln | missense_variant | 12/13 | 1 | NM_017802.4 | ENSP00000297440 | P1 | |
DNAAF5 | ENST00000403952.3 | c.650G>A | p.Arg217Gln | missense_variant | 5/6 | 1 | ENSP00000384884 | |||
DNAAF5 | ENST00000440747.5 | c.1781G>A | p.Arg594Gln | missense_variant | 12/13 | 2 | ENSP00000403165 | |||
DNAAF5 | ENST00000461576.1 | n.185G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251358Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135840
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.0000715 AC XY: 52AN XY: 727230
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2022 | The p.R792Q variant (also known as c.2375G>A), located in coding exon 12 of the DNAAF5 gene, results from a G to A substitution at nucleotide position 2375. The arginine at codon 792 is replaced by glutamine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 21, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 792 of the DNAAF5 protein (p.Arg792Gln). This variant is present in population databases (rs772102523, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with DNAAF5-related conditions. ClinVar contains an entry for this variant (Variation ID: 410301). 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. 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. - |
DNAAF5-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 06, 2024 | The DNAAF5 c.2375G>A variant is predicted to result in the amino acid substitution p.Arg792Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at