rs150672056
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_178452.6(DNAAF1):āc.604A>Gā(p.Met202Val) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,614,052 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 ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 32)
Exomes š: 0.00016 ( 0 hom. )
Consequence
DNAAF1
NM_178452.6 missense
NM_178452.6 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.70
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1275363).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.604A>G | p.Met202Val | missense_variant | 5/12 | ENST00000378553.10 | NP_848547.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.604A>G | p.Met202Val | missense_variant | 5/12 | 1 | NM_178452.6 | ENSP00000367815.5 | ||
DNAAF1 | ENST00000567918.5 | n.604A>G | non_coding_transcript_exon_variant | 5/7 | 1 | ENSP00000455154.1 | ||||
DNAAF1 | ENST00000563093.5 | n.604A>G | non_coding_transcript_exon_variant | 5/11 | 2 | ENSP00000457373.1 | ||||
DNAAF1 | ENST00000570298.5 | n.758A>G | non_coding_transcript_exon_variant | 5/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251490Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135918
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GnomAD4 exome AF: 0.000163 AC: 239AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 109AN XY: 727244
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 16, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 202 of the DNAAF1 protein (p.Met202Val). This variant is present in population databases (rs150672056, gnomAD 0.03%). This missense change has been observed in individual(s) with multiple congenital anomalies (PMID: 26633542). ClinVar contains an entry for this variant (Variation ID: 574291). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2023 | The p.M202V variant (also known as c.604A>G), located in coding exon 5 of the DNAAF1 gene, results from an A to G substitution at nucleotide position 604. The methionine at codon 202 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 03, 2024 | BP4, BP5 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at