rs760933549
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018139.3(DNAAF2):āc.1129G>Cā(p.Gly377Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,522,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G377V) has been classified 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.1129G>C | p.Gly377Arg | missense_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.1129G>C | p.Gly377Arg | missense_variant | 1/2 | ||
DNAAF2 | NM_001378453.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.1129G>C | p.Gly377Arg | missense_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.1129G>C | p.Gly377Arg | missense_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000130 AC: 15AN: 115020Hom.: 0 AF XY: 0.000158 AC XY: 10AN XY: 63162
GnomAD4 exome AF: 0.000292 AC: 400AN: 1370448Hom.: 0 Cov.: 89 AF XY: 0.000308 AC XY: 208AN XY: 675622
GnomAD4 genome ? AF: 0.000250 AC: 38AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24AN XY: 74344
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.1129G>C (p.G377R) alteration is located in exon 1 (coding exon 1) of the DNAAF2 gene. This alteration results from a G to C substitution at nucleotide position 1129, causing the glycine (G) at amino acid position 377 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 377 of the DNAAF2 protein (p.Gly377Arg). This variant is present in population databases (rs760933549, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DNAAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 411170). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 28, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 23, 2023 | BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at