Genetic Variant DNAAF2:p.Ser8* (chr14-49635127-G-T) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_018139.3(DNAAF2):c.23C>A(p.Ser8*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000283 in 1,411,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DNAAF2
NM_018139.3 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.87

Publications

8 publications found

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]

DNAAF2 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 10
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 46 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-49635127-G-T is Pathogenic according to our data. Variant chr14-49635127-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 529.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF2	NM_018139.3 link	c.23C>A	p.Ser8*	stop_gained	Exon 1 of 3	ENST00000298292.13	NP_060609.2	Q9NVR5-1
DNAAF2	NM_001083908.2 link	c.23C>A	p.Ser8*	stop_gained	Exon 1 of 2		NP_001077377.1	Q9NVR5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13 link	c.23C>A	p.Ser8*	stop_gained	Exon 1 of 3	1	NM_018139.3	ENSP00000298292.8		Q9NVR5-1
DNAAF2	ENST00000406043.3 link	c.23C>A	p.Ser8*	stop_gained	Exon 1 of 2	1		ENSP00000384862.3		Q9NVR5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1411476

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32170

American (AMR)

AF:

0.00

AC:

AN:

37328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25338

East Asian (EAS)

AF:

0.00

AC:

AN:

36634

South Asian (SAS)

AF:

0.00

AC:

AN:

80194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48756

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00000276

AC:

AN:

1086896

Other (OTH)

AF:

0.00

AC:

AN:

58490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 10

Pathogenic:1

Dec 04, 2008

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Kartagener syndrome

Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.89

PhyloP100

4.9

Vest4

0.11

GERP RS

5.3

PromoterAI

0.034

Neutral

(source)

Mutation Taster

=5/195

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over