14-49634055-CGCGGCG-CGCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000298292.13(DNAAF2):​c.1092_1094del​(p.Ala365del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,368,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

DNAAF2
ENST00000298292.13 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.523
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAAF2NM_018139.3 linkuse as main transcriptc.1092_1094del p.Ala365del inframe_deletion 1/3 ENST00000298292.13 NP_060609.2
DNAAF2NM_001083908.2 linkuse as main transcriptc.1092_1094del p.Ala365del inframe_deletion 1/2 NP_001077377.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAAF2ENST00000298292.13 linkuse as main transcriptc.1092_1094del p.Ala365del inframe_deletion 1/31 NM_018139.3 ENSP00000298292 P2Q9NVR5-1
DNAAF2ENST00000406043.3 linkuse as main transcriptc.1092_1094del p.Ala365del inframe_deletion 1/21 ENSP00000384862 A2Q9NVR5-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000439
AC:
6
AN:
1368252
Hom.:
0
AF XY:
0.00000445
AC XY:
3
AN XY:
673808
show subpopulations
Gnomad4 AFR exome
AF:
0.0000653
Gnomad4 AMR exome
AF:
0.0000308
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000283
Gnomad4 SAS exome
AF:
0.0000265
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 05, 2022This variant, c.1092_1094del, results in the deletion of 1 amino acid(s) of the DNAAF2 protein (p.Ala365del), but otherwise preserves the integrity of the reading frame. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 572785). This variant has not been reported in the literature in individuals affected with DNAAF2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745419780; hg19: chr14-50100773; API