rs761527467
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018139.3(DNAAF2):c.416A>G(p.Tyr139Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,604,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Y139Y) has been classified as Likely benign.
Frequency
Consequence
NM_018139.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.416A>G | p.Tyr139Cys | missense_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.416A>G | p.Tyr139Cys | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.416A>G | p.Tyr139Cys | missense_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.416A>G | p.Tyr139Cys | missense_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152220Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000614 AC: 14AN: 227994Hom.: 0 AF XY: 0.0000634 AC XY: 8AN XY: 126268
GnomAD4 exome AF: 0.0000689 AC: 100AN: 1452324Hom.: 0 Cov.: 98 AF XY: 0.0000775 AC XY: 56AN XY: 722776
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152220Hom.: 0 Cov.: 35 AF XY: 0.0000672 AC XY: 5AN XY: 74380
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 28, 2021 | - - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2022 | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 454909). This variant has not been reported in the literature in individuals affected with DNAAF2-related conditions. This variant is present in population databases (rs761527467, gnomAD 0.01%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 139 of the DNAAF2 protein (p.Tyr139Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at