chr14-49633656-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_018139.3(DNAAF2):c.1494G>A(p.Ser498Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,612,306 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0048 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0030 ( 33 hom. )
Consequence
DNAAF2
NM_018139.3 synonymous
NM_018139.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.970
Genes affected
DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 14-49633656-C-T is Benign according to our data. Variant chr14-49633656-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261013.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2, Benign=4}. Variant chr14-49633656-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.97 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00477 (726/152320) while in subpopulation SAS AF= 0.00621 (30/4830). AF 95% confidence interval is 0.00461. There are 7 homozygotes in gnomad4. There are 441 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DNAAF2 | NM_018139.3 | c.1494G>A | p.Ser498Ser | synonymous_variant | 1/3 | ENST00000298292.13 | NP_060609.2 | |
| DNAAF2 | NM_001083908.2 | c.1494G>A | p.Ser498Ser | synonymous_variant | 1/2 | NP_001077377.1 | ||
| DNAAF2 | NM_001378453.1 | c.-378G>A | 5_prime_UTR_variant | 1/2 | NP_001365382.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00471 AC: 717AN: 152202Hom.: 6 Cov.: 33
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GnomAD3 exomes AF: 0.00510 AC: 1270AN: 249192Hom.: 14 AF XY: 0.00505 AC XY: 682AN XY: 135148
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GnomAD4 exome AF: 0.00304 AC: 4433AN: 1459986Hom.: 33 Cov.: 31 AF XY: 0.00315 AC XY: 2288AN XY: 726106
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GnomAD4 genome 0.00477 AC: 726AN: 152320Hom.: 7 Cov.: 33 AF XY: 0.00592 AC XY: 441AN XY: 74496
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 10 Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
| Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 31, 2022 | - - |
not specified Benign:2
| Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
| Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Ser498Ser in exon 1 of DNAAF2: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.5% (20/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2985688). - |
Primary ciliary dyskinesia Benign:2
| Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2014 | This alteration is classified as likely 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. - |
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2025 | - - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | DNAAF2: BP4, BP7, BS2 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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