14-49625566-AT-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_018139.3(DNAAF2):c.2489del(p.Asn830IlefsTer12) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N830N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF2 NM_018139.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 904 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF2	NM_018139.3	c.2489del	p.Asn830IlefsTer12	frameshift_variant	3/3	ENST00000298292.13
DNAAF2	NM_001083908.2	c.2345del	p.Asn782IlefsTer12	frameshift_variant	2/2
DNAAF2	NM_001378453.1	c.278del	p.Asn93IlefsTer12	frameshift_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF2	ENST00000298292.13	c.2489del	p.Asn830IlefsTer12	frameshift_variant	3/3	1	NM_018139.3	P2
DNAAF2	ENST00000406043.3	c.2345del	p.Asn782IlefsTer12	frameshift_variant	2/2	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 04, 2022

This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DNAAF2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. This sequence change results in a frameshift in the DNAAF2 gene (p.Asn830Ilefs*12). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 8 amino acid(s) of the DNAAF2 protein and extend the protein by 3 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-50092284;