14-49633691-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_018139.3(DNAAF2):c.1459C>T(p.Arg487Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,605,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_018139.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.1459C>T | p.Arg487Cys | missense_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.1459C>T | p.Arg487Cys | missense_variant | 1/2 | ||
DNAAF2 | NM_001378453.1 | c.-413C>T | 5_prime_UTR_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.1459C>T | p.Arg487Cys | missense_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.1459C>T | p.Arg487Cys | missense_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000933 AC: 142AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000317 AC: 78AN: 245934Hom.: 0 AF XY: 0.000217 AC XY: 29AN XY: 133706
GnomAD4 exome AF: 0.000140 AC: 204AN: 1453328Hom.: 0 Cov.: 92 AF XY: 0.000115 AC XY: 83AN XY: 721802
GnomAD4 genome AF: 0.000933 AC: 142AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.000900 AC XY: 67AN XY: 74448
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
DNAAF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 04, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at